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Fibrosis is characterized by excessive extracellular matrix (ECM) deposition resulting from dysregulated wound healing and connective tissue repair mechanisms. Excessive accumulation of ECM leads to fibrous tissue formation, impairing organ function and driving the progression of various fibrotic diseases. Recently, the role of small ubiquitin-like modifiers (SUMO) in fibrotic diseases has attracted significant attention. SUMO-mediated SUMOylation, a highly conserved posttranslational modification, participates in a variety of biological processes, including nuclear-cytosolic transport, cell cycle progression, DNA damage repair, and cellular metabolism. Conversely, SUMO-specific proteases cleave the isopeptide bond of SUMO conjugates, thereby regulating the deSUMOylation process. Mounting evidence indicates that SUMOylation and deSUMOylation regulate the functions of several proteins, such as Smad3, NF-κB, and promyelocytic leukemia protein, which are implicated in fibrotic diseases like liver fibrosis, myocardial fibrosis, and pulmonary fibrosis. This review summarizes the role of SUMO in fibrosis-related pathways and explores its pathological relevance in various fibrotic diseases. All evidence suggest that the SUMO pathway is important targets for the development of treatments for fibrotic diseases., (© 2024 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.)

β-arrestin2, a pivotal protein within the arrestin family, is localized in the cytoplasm, plasma membrane and nucleus, and regulates G protein-coupled receptors (GPCRs) signaling. Recent evidence shows that β-arrestin2 plays a dual role in regulating GPCRs by mediating desensitization and internalization, and by acting as a scaffold for the internalization, kinase activation, and the modulation of various signaling pathways, including NF-κB, MAPK, and TGF-β pathways of non-GPCRs. Earlier studies have identified that β-arrestin2 is essential in regulating immune cell infiltration, inflammatory factor release, and inflammatory cell proliferation. Evidently, β-arrestin2 is integral to the pathological mechanisms of inflammatory immune diseases, such as inflammatory bowel disease, sepsis, asthma, rheumatoid arthritis, organ fibrosis, and tumors. Research on the modulation of β-arrestin2 offers a promising strategy for the development of pharmaceuticals targeting inflammatory immune diseases. This review meticulously describes the roles of β-arrestin2 in cells associated with inflammatory immune responses and explores its pathological relevance in various inflammatory immune diseases., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

A two-step method for preparing composite coatings with different composition on Ti alloys using softened spark microarc oxidation technology was proposed. The nucleation and growth processes of a softened spark layer, as well as the influence of softened sparks on the deposition of anions in electrolytes, were studied. The results show that the process voltage of the softened spark discharge on the selective laser-melted Ti6Al4V alloy was lower than the breakdown voltage of its anodic oxide film. The softened sparks prioritized nucleation at the coating/substrate interface in the initial spark discharge area rather than in the microarc discharge area. On one hand, the softened spark layer grew towards the Ti6Al4V substrate, and on the other hand, the molten oxide generated by the softened sparking was transferred into the external porous layer. The softened sparks generated inside the coating promoted the rutile phase formation and linear growth in the thickness of the softened spark layer. Ca and P are mainly distributed in the external porous layer or at the interface between the softened-spark and external porous layers. Nevertheless, softened sparking had little effect on the initial micro/nanoporous structures of the coatings., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Pediatric intestinal development is immature, vulnerable to external influences and produce a variety of intestinal diseases. At present, breakthroughs have been made in the treatment of pediatric intestinal diseases, but there are still many challenges, such as toxic side effects, drug resistance, and the lack of more effective treatments and specific drugs. In recent years, dietary polyphenols derived from plants have become a research hotspot in the treatment of pediatric intestinal diseases due to their outstanding pharmacological activities such, as anti-inflammatory, antibacterial, antioxidant and regulation of intestinal flora. This article reviewed the mechanism of action and clinical evidence of dietary polyphenols in the treatment of pediatric intestinal diseases, and discussed the influence of physiological characteristics of children on the efficacy of polyphenols, and finally prospected the new dosage forms of polyphenols in pediatrics., (© 2024 John Wiley & Sons Ltd.)

Ethnopharmacological Relevance: The Antiviral Granules (AG) are derived from the classical famous prescription, which is composed of 9 traditional Chinese medicines, namely Radix Isatidis (called Banlangen, BLG in Chinese), Forsythiae Fructus (called Lianqiao, LQ in Chinese), Gypsum fibrosum, Anemarrhenae Rhizoma (called Zhimu, ZM in Chinese), Phragmitis Rhizoma (called Lugen, LG in Chinese), Rehmanniae Radix (called Dihuang, DH in Chinese), Pogostemonis Herba (called Guanghuoxiang, GHX in Chinese), Acori Tatarinowii Rhizoma (called Shichangpu, SCP in Chinese), and Curcumae Radix (called Yujin, YJ in Chinese), and has shown an excellent therapeutic effect in clinical treatment of influenza. However, there are few studies on the anti-influenza mechanism of AG, and the mechanism of action is still unclear., Aim of the Study: The purpose is to provide the latest information about the clinical efficacy, pharmacodynamic composition and mechanism of AG based on scientific literature, so as to enhance the utilization of AG in the treatment of influenza and related diseases, and promote the development and innovation of novel anti-influenza drugs targeting the influenza virus., Materials and Methods: Enter the data retrieval room, search for Antiviral Granules, as well as the scientific names, common names, and Chinese names of each Chinese medicine. Additionally, search for the relevant clinical applications, pharmacodynamic composition, pharmacological action, and molecular mechanism of both Antiviral Granules and single-ingredient medicines. Keywords includes terms such as "antiviral granules", "influenza", "Isatis indigotica Fort.", "Radix Isatidis", "Banlangeng", "pharmacology", "clinical application", "pharmacologic action", etc. and their combinations. Obtain results from the Web of Science, PubMed, Google Scholar, Sci Finder Scholar, CNKI and other resources., Results: AG is effective in the treatment of influenza and is often used in combination with other drugs to treat viral diseases. Its chemical composition is complex, including alkaloids, polysaccharides, volatile oils, steroid saponins, phenylpropanoids, terpenoids and other compounds. These compounds have a variety of pharmacological activities, which can interfere with the replication cycle of the influenza virus, regulate RIG-I-MAVS, JAK/STAT, TLRs/MyD88, NF-κB signaling pathways and related cytokines, regulate intestinal microorganisms, and protect both the lungs and extrapulmonary organs., Conclusions: AG can overcome the limitations of traditional antiviral drug therapy, play a synergistic role in fighting influenza virus with the characteristics of multi-component, multi-pathway and multi-target therapy, and reverse the bodily function damage caused by influenza virus. AG may be a potential drug in the prevention and treatment of influenza and related diseases., 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 © 2023 Elsevier B.V. All rights reserved.)

Objective: In the present study, we aimed to investigate the effects of enzymolysis fermentation of Chinese herbal medicines (CHMs) on egg production performance, egg quality, lipid metabolism, serum reproductive hormone levels, and the mRNA expression of the ovarian hormone receptor of laying hens in the late-laying stage., Methods: A total of 360 Hy-Line Brown laying hens (age, 390 days) were randomly categorized into four groups. Hens in the control (C) group were fed a basic diet devoid of CHMs, the crushed CHM (CT), fermented CHM (FC), and enzymatically fermented CHM (EFT) groups received diets containing 2% crushed CHM, 2% fermented CHM, and 2% enzymatically fermented CHM, respectively., Results: Compared with crushed CHM, the acid detergent fiber, total flavonoids, and total saponins contents of fermented CHM showed improvement (p<0.05); furthermore, the neutral and acid detergent fiber, total flavonoids, and total saponins contents of enzymatically fermented CHM improved (p<0.05). At 5 to 8 weeks, hens in the FC and EFT groups showed increased laying rates, haugh unit, albumin height, yolk color, shell thickness, and shell strength compared with those in the C group (p<0.05). Compared with the FC group, the laying rate, albumin height, and Shell thickness in the EFT group was increased (p<0.05). Compared with the C, CT, and FC groups, the EFT group showed reduced serum total cholesterol and increased serum luteinizing hormone levels and mRNA expressions of follicle stimulating hormone receptor and luteinizing hormone receptor (p<0.05)., Conclusion: These results indicated that the ETF group improved the laying rate and egg quality and regulated the lipid metabolism in aged hens. The mechanism underlying this effect was likely related to cell wall degradation of CHM and increased serum levels of luteinizing hormone and mRNA expression of the ovarian hormone receptor.

Purpose: To explore the molecular mechanism of circ&#95;0000326 regulating proliferation, invasion and migration of oral squamous cell carcinoma HSC3 cells., Methods: Cancerous tissue and adjacent tissue specimens of 45 patients with oral squamous cell carcinoma (OSCC) admitted to the Second People's Hospital of Hefei from March 2020 to June 2021 were collected. qRT-PCR was used to detect the expression levels of circ&#95;0000326 and miR-567. CCK-8, plate clone formation test, scratch test and Transwell test were used to detect cell proliferation, clone formation, migration and invasion. Dual luciferase reporter experiment was used to detect the targeting relationship between circ&#95;0000326 and miR-567. Western blot was used to quantify E-cadherin and N-cadherin protein. SPSS 21.0 software package was used for statistical analysis., Results: circ&#95;0000326 expression was 4.01±0.29 in OSCC and 1.00±0.13 in paracancerous tissues, while miR-567 expression was 0.28±0.03 and 1.00±0.10, respectively, with significant differences. Compared with the si-NC group, the cell viability and the number of cell clones in the si-circ&#95;0000326 group were significantly decreased(P＜0.05). Compared with the si-NC group, the number of invasive cells and scratch healing rate in the si-circ&#95;0000326 group were significantly decreased (P＜0.05), the expression level of E-cadherin protein was significantly increased (P＜0.05), and the expression level of N-cadherin protein was significantly decreased(P＜0.05). Additionally, circ&#95;0000326 targeted miR-567. miR-567 expression was 1.00±0.00 in pcDNA group, 0.44±0.04 in pcDNA-circ&#95;0000326 group, 0.99±0.06 in si-NC group, and 2.92±0.25 in si-circ&#95;0000326 group with significant differences. Compared with miR-NC group, the cell viability, scratch healing rate, the number of cell clones and the number of invasive cells of miR-567 group were decreased, while E-cadherin protein level was increased(P＜0.05). Compared with si-circ&#95;0000326+anti-miR-NC group, the cell viability, scratch healing rate, N-cadherin protein level, the number of cell clones and the number of invasive cells of si-circ&#95;0000326+anti-miR-567 group were increased(P＜0.05), while E-cadherin protein level was decreased(P＜0.05)., Conclusions: Interference with the expression of circ&#95;0000326 could reduce the ability of OSCC cell proliferation, colony formation, migration and invasion by promoting the expression of miR-567.

Objectives: Primary biliary cholangitis (PBC) is a rare disease characterized by intrahepatic cholestasis, whereas gallstone disease (GD) is common. In this study, we aimed to investigate the prevalence and impact of GD on the prognosis of PBC in China., Methods: Medical records of the PBC patients were retrospectively reviewed and their follow-up data were obtained via regular structured, standardized telephone interviews. GD was defined as gallstones on ultrasonography or a history of cholecystectomy for gallstones. Propensity score matching (PSM) and Cox regression analysis were performed. The primary end-point was liver-related death and/or liver transplantation., Results: A total of 985 ursodeoxycholic acid (UDCA)-treated PBC patients were enrolled with a median follow-up duration of 5.3 years (range 1.0-20.9 years). Among them, 258 (26.2%) had GD, including 157 (22.9%) of non-cirrhotic and 101 (33.8%) of cirrhotic patients. Compared with PBC without GD, those with GD were older, more often had type 2 diabetes mellitus, and had a more severe liver disease at baseline. After PSM (1:2), 229 PBC patients with GD were matched with 458 PBC patients without GD based on age, sex, cirrhosis, and total bilirubin level. The transplant-free survival and incidence of hepatic events were similar between the two groups. Furthermore, multivariate Cox regression analysis showed that concomitant GD was not independently associated with a worse prognosis for PBC patients., Conclusion: Concomitant GD was common but was not associated with long-term outcomes in patients with UDCA-treated PBC., (© 2023 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background: Primary biliary cholangitis (PBC) patients often have concomitant extrahepatic autoimmune (EHA) diseases including Sjögren's syndrome (SS), systemic sclerosis (SSc), rheumatoid arthritis (RA), and autoimmune thyroid disease. The present study aimed to describe the prevalence of EHA diseases in PBC and explore the impact of EHA diseases on the long-term outcomes of PBC in Chinese patients., Methods: Medical records of PBC patients diagnosed in our institute were retrospectively reviewed. Patients were followed up by a standardized telephone interview. The endpoints were defined as liver-related death and/or liver transplantation., Results: Totally 247 of the 985 (25.1%) PBC patients enrolled in the study had at least one concomitant EHA disease. Sjögren's syndrome (n = 140, 14.2%) was the most frequent one, followed by rheumatoid arthritis (RA) (n = 56, 5.7%) and Hashimoto's thyroiditis (n = 45, 4.6%). Patients with EHA diseases were more common in females (P < 0.001) and in those with a family history of autoimmune disease (P = 0.017). Overall, no differences were found between PBC patients with and without EHA diseases in terms of biochemical response rates to ursodeoxycholic acid, the incidence of hepatic events, or transplant-free survival. RA and EHA ≥ 2 were protective factors for hepatic events in univariate Cox analysis, but the results became insignificant in multivariate analysis., Conclusions: Concomitant EHA diseases were common in PBC patients but did not compromise the long-term outcomes of PBC., (Copyright © 2022. Published by Elsevier B.V.)

Hepatitis A virus (HAV) live-attenuated vaccine H2 strain has been approved for clinical use for decades with ideal safety profiles in nonhuman primate models and humans. Recently, type I interferon (IFN) receptor-deficient mice were shown to be susceptible to HAV infection. Herein, we sought to determine the infection and replication dynamics of the H2 in Ifnar -/- mice that lack type I IFN receptor. Following intravenous injection, the H2 failed to cause obvious clinical symptoms in Ifnar -/- mice, and no significant upregulation in serum alanine aminotransferase (ALT) levels was observed. Notably, the histopathological examination showed that there were significant focal infiltrations of lymphocytes and neutrophils in the portal area, but no focal necrosis was observed in liver tissues. Viral RNAs sustained in the liver, and the infectious virus could be recovered from the liver tissue until 42 days post-infection. More importantly, H2 infection induced obvious viremia and persistent viral shedding in feces. In addition, robust HAV-specific humoral immune responses were induced in Ifnar -/- mice. Overall, our study revealed the safety profile of H2 in Ifnar -/- mice, which not only helps understand the attenuation mechanism of H2, but also expands the application of the Ifnar -/- mouse model for HAV studies., (Copyright © 2022 The Authors. Publishing services by Elsevier B.V. All rights reserved.)

Phyllanthi Fructus, a unique Chinese and Tibetan medicinal plant with both edible and medical values, has high potential of cultivation and development. The resources of Phyllanthi Fructus in China are rich, mainly distributed in Yunnan, Sichuan, Fujian, Guangdong, Guangxi, etc. Phyllanthi Fructus is widely used in the clinical practice of Chinese medicine and plays an important role in Tibetan medicine, Uyghur medicine, Yi medicine, and Mongolian medicine. Phyllanthi Fructus mainly contains phenolic acids,tannins, terpenes, sterols, fatty acids, flavonoids, amino acids and other compounds. Modern pharmacological studies show that Phyllanthi Fructus has antioxidant, anticancer, blood lipid-lowering, liver protective, antimicrobial, anti-inflammatory, and immune regulatory activities. In this paper, the research status of Phyllanthi Fructus was reviewed from the aspects of herbal textual research,chemical composition, and pharmacological action. The quality markers(Q-markers) of Phyllanthi Fructus were predicted and analyzed from the aspects of biogenic pathway, specificity and measurability of chemical components, efficacy, properties, new clinical uses, drug-food homology, and transformation of polyphenols. The results will provide a scientific basis for the quality control, quality evaluation, and standard formulation of Phyllanthi Fructus.

Phyllanthus emblica is a fruit widely consumed in subtropical areas, which is rich in polyphenols and other nutrients. There are increasing evidences that as a daily and nutritious fruit, it may have a positive role in controlling diabetic complications. According to the new study, its mechanisms include enhancing the functioning of insulin, reducing insulin resistance, activating the insulin-signaling pathway, protecting β-cells, scavenging free radicals, alleviating inflammatory reactions, and reducing the accumulation of advanced glycation end products. Owing to its few side effects, and low price, it should be easily accepted by patients and has potential for preventing diabetes. Taken together, Phyllanthus emblica may be an ideal fruit for controlling diabetic complications. This review highlights the latest findings of the role of Phyllanthus emblica in anti-diabetes and its complications, especially clarifies the molecular mechanism of the chemical components related to this effect, and prospects some existing problems and future research directions., (© 2021. Springer-Verlag GmbH, DE part of Springer Nature.)

Background: The pandemic of coronavirus disease 2019 (COVID-19) has global impact, Wuhan in Hubei province is a high-risk area. And the older people in nursing homes are the most susceptible group to COVID-19. The aim of this study was to describe the practice and experience of the first-line medical team, to provide insights of coping with COVID-19 in China., Method: This qualitative study used a descriptive phenomenological design to describe the experience of medical staff supported the nursing homes in Wuhan fighting against COVID-19. Unstructured interviews via online video were conducted with seven medical staffs who supported the nursing homes in Wuhan. Data were analyzed using content analysis in five main themes: for nursing homes, we interviewed the difficulties faced at the most difficult time, services for the older people, and prevention and management strategies, for the medical staff, the psychological experience were interviewed, and the implications for public health emergencies were also reported., Conclusions: It is imperative that effective preventive and response measures be implemented to face the outbreak of COVID-19 and meet the care needs of older people in the context of COVID-19., Implications: Findings will inform managers of some reasonable instructional strategies for implementing effective infection management. Nursing homes need to provide targeted services to help alleviating their bad psychology for residents., Competing Interests: The authors have declared that no competing interests exist.

The peritoneal implant metastasis is one of the main pathway and main cause for high mortality for gastric cancer metastasis. Researchs show that epithelial-mesenchymal transition (EMT) playing essential role in modulating gastric cancer metastasis, and the expression of hypoxia inducible factor-1α (HIF-1α) can promote EMT in tumor cells. This research aims to explore the influence and mechanism of Dextran Sulfate (DS) affecting EMT of human gastric cancer. In the present study, we found that DS can enter into the cytoplasm and function in it. Inhibition of HIF-1α or DS significantly inhibit the migration and invasion of human gastric cancer cells, and decrease the mRNA and protein expressions of HIF-1α, matrix metalloproteinase-2 (MMP-2), transforming growth factor-β (TGF-β), Twist and N-cadherin (N-cad), rise E-cadherin (E-cad) expression, DS with HIF-1α knockdown has a stronger effect. In vivo studies indicated that compared with using DS or HIF-1α knockdown alone, DS with HIF-1α knockdown can better suppress the volume and number of metastatic tumors, and reduce the mRNA and protein expressions of HIF-1α, MMP-2, TGF-β, Twist and N-cad in metastatic tumor tissues of nude mice. We further demonstrated that the expression of HIF-1α, MMP-2, TGF-β , Twist and N-cad were higher in well and poorly differentiated gastric cancer than paracancerous tissue, and poorly differentiated gastric cancer were even higher, while E-cad expression was opposite. Taken together, this study shows that DS can interfere the expression of HIF-1α, thereby inhibiting TGF-β-mediated EMT of gastric cancer cells, and demonstrated a promising application of DS in gastric cancer therapy., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Phyllanthus emblica is a kind of traditional medicine and medicinal and edible plant, with rich variety resources and high development value. It is a key poverty alleviation variety in China at present. As P. emblica processing industry is rising gradually in recent years, in order to fully develop and utilize its industrial resources, this paper systematically introduces current comprehensive development and utilization of P. emblica, discusses the problems in P. emblica processing industry, and puts forward comprehensive development and utilization strategies and industrial models in terms of cultivation, breeding, grading, quality evaluation and waste recycling, so as to provide a certain reference for promoting the high-quality development of P. emblica industry in China.

Neuropathic pain is still a critical public health problem worldwide. Thereby, the search for novel and more effective strategies against neuropathic pain is urgently considered. It is known that neuroinflammation plays a crucial role in the pathogenesis of neuropathic pain. SedumLineare Thunb. (SLT), a kind of Chinese herb originated from the whole grass of Crassulaceae plant, was reported to possess anti-inflammatory activity. However, whether SLT has anti-nociceptive effect on neuropathic pain and its possible underlying mechanisms remains poorly elucidated. In this study, a rat model of neuropathic pain induced by spared nerve injury (SNI)was applied. SLT (p.o.) was administered to SNI rats once every day lasting for 14 days. Pain-related behaviors were assessed by using paw withdrawal threshold (PWT) and CatWalk gait parameters. Expression levels of inflammatory mediators and pain-related signaling molecules in the spinal cord were detected using western blotting assay. The results revealed that SLT (30, 100, and 300 mg/kg, p.o.) treatment for SNI rats ameliorated mechanical hypersensitivity in a dose-dependent manner. Application of SLT at the most effective dose of 100 mg/kg to SNI rats not only significantly blocked microglial activation, but also markedly reduced the protein levels of spinal HMGB1, TLR4, MyD88, TRAF6, IL-1β, IL-6, and TNF-α, along with an enhancement in gait parameters. Furthermore, SLT treatment dramatically inhibited the phosphorylation levels of both IKK and NF-κB p65 but obviously improved both IκB and IL-10 protein expression in the spinal cord of SNI rats. Altogether, these data suggested that SLT could suppress spinal TLR4/NF-κB signaling pathway in SNI rats, which might at least partly contribute to its anti-nociceptive action, indicating that SLT may serveas a potential therapeutic agent for neuropathic pain., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The development of atherosclerosis is accompanied by the functional deterioration of plaque cells, which leads to the escalation of endothelial inflammation, abnormal vascular smooth muscle cell phenotype switching and the accumulation of lipid-laden macrophages within vascular walls. Autophagy, a highly conserved homeostatic mechanism, is critical for the delivery of cytoplasmic substrates to lysosomes for degradation. Moderate levels of autophagy prevent atherosclerosis by safeguarding plaque cells against apoptosis, preventing inflammation, and limiting the lipid burden, whereas excessive autophagy exacerbates cell damage and inflammation and thereby accelerates the formation of atherosclerotic plaques. Increasing lines of evidence suggest that long noncoding RNAs can be either beneficial or detrimental to atherosclerosis development by regulating the autophagy level. This review summarizes the research progress related to 1) the significant role of autophagy in atherosclerosis and 2) the effects of the lncRNA-mediated modulation of autophagy on the plaque cell fate, inflammation levels, proliferative capacity, and cholesterol metabolism and subsequently on atherogenesis.

Leaf angle is a key factor in plant architecture and crop yield. Brassinosteroids (BRs) regulate many developmental processes, especially the leaf angle in monocots. However, the BR signalling pathway is complex and includes many unknown members. Here, we propose that Oryza sativa BRASSINOSTEROID-RESPONSIVE LEAF ANGLE REGULATOR 1 (OsBLR1) encodes a bHLH transcription factor, and positively regulates BR signalling to increase the leaf angle and grain length in rice (Oryza sativa L.). Lines overexpressing OsBLR1 (blr1-D and BLR1-OE-1/2/3) had similar traits, with increased leaf angle and grain length. Conversely, OsBLR1-knockout mutants (blr1-1/2/3) had erect leaves and shorter grains. Lamina joint inclination, coleoptile elongation, and root elongation assay results indicated that these overexpression lines were more sensitive to BR, while the knockout mutants were less sensitive. There was no significant difference in the endogenous BR contents of blr1-1/2 and wild-type plants. These results suggest that OsBLR1 is involved in BR signal transduction. The blr1-D mutant, with increased cell growth in the lamina joint and smaller leaf midrib, showed significant changes in gene expression related to the cell wall and leaf development compared with wild-type plants; furthermore, the cellulose and protopectin contents in blr1-D were reduced, which resulted in the increased leaf angle and bent leaves. As the potential downstream target gene of OsBLR1, the REGULATOR OF LEAF INCLINATION1 (OsRLI1) gene expression was up-regulated in OsBLR1-overexpression lines and down-regulated in OsBLR1-knockout mutants. Moreover, we screened OsRACK1A as an interaction protein of OsBLR1 using a yeast two-hybrid assay and glutathione-S-transferase pull-down.

When ultraviolet (UV) absorption spectroscopy technology is used for nitric oxide (NO) detection, the background noise will directly affect the accuracy of concentration inversion, especially in low concentrations. Traditional processing methods attempt to eliminate background noise, which damages the absorption spectrum characteristics. However, stochastic resonance (SR) can utilize the noise to extract a weak characteristic signal. This paper reports a monostable stochastic resonance (MSR) model for processing an UV NO absorption spectrum. By analyzing the characteristics of UV absorption spectrum of NO, the evaluation indexes were constructed, thereby an adaptive MSR method was designed for parameter optimization. The numerical simulation confirmed the absorbance peak can be amplified and spectral signal-to-noise ratio (SNR) can be in the stable range of the proposed method, when noise intensity increased. Finally, this experiment obtained a NO detection limit (3σ) of 1.456 ppm and the maximum relative deviation of concentration is 6.32% by this proposed method, which is satisfactory for processing of the UV NO absorption spectrum.

Understanding the regulation of proline metabolism necessitates the suppression of two Δ 1 -pyrroline-5-carboxylate synthetase enzyme ( P5CS ) genes performed in switchgrass ( Panicum virgatum L.). The results reveal that overexpressing PvP5CS1 and PvP5CS2 increased salt tolerance. Additionally, transcript levels of spermidine (Spd) and spermine (Spm) synthesis and metabolism related genes were upregulated in PvP5CS OE -transgenic plants and downregulated in the PvP5CS RNAi transformants. According to salt stress assay and the measurement of transcript levels of Polyamines (PAs) metabolism-related genes, P5CS enzyme may not only be the key regulator of proline biosynthesis in switchgrass, but it may also indirectly affect the entire subset of pathway for ornithine to proline or to putrescine (Put). Furthermore, application of proline prompted expression levels of Spd and Spm synthesis and metabolism-related genes in both PvP5CS - RNAi and WT plants, but transcript levels were even lower in PvP5CS - RNAi compared to WT plants under salt stress condition. These results suggested that exogenous proline could accelerate polyamines metabolisms under salt stress. Nevertheless, the enzymes involved in this process and the potential functions remain poorly understood. Thus, the aim of this study is to reveal how proline functions with PAs metabolism under salt stress in switchgrass., (Copyright © 2020 Guan, Cui, Liu, Li, Li and Zhang.)

Objective: The purpose of the present study was to conduct a meta-analysis to systematically compare the incidence rates of in-stent restenosis after carotid artery stenting (CAS) and restenosis after carotid endarterectomy (CEA) for patients with atherosclerotic carotid stenosis., Methods: We retrieved potential academic reports comparing restenosis between CEA and CAS from the MEDLINE, PubMed, and EMBASE databases and the Cochrane Library from the date of the first CEA (January 1951) to July 20, 2018. The references of the identified studies were carefully reviewed to ensure that all available reports were included in the present study., Results: Our meta-analysis included 27 studies (15 randomized controlled trials, 12 nonrandomized controlled trials) and 20,479 participants with atherosclerotic carotid stenosis. A statistically significant difference was found in the cumulative incidence of restenosis >70% between CEA and CAS (risk difference, -0.033, 95% confidence interval [CI] -0.054 to -0.013; P = 0.002). For the restenosis >70% outcomes, although CEA was relevant with a lower rate of restenosis than CAS within 6 months (odds ratio [OR], 0.495; 95% CI, 0.285-0.861; P = 0.013) and 1 year (OR, 0.626; 95% CI, 0.483-0.811; P < 0.001), no statistically significant differences were found at 1.5 years (P = 0.210), 2 years (P = 0.123), 4 years (P = 0.124), 5 years (P = 0.327), or 10 years (P = 0.839). For the restenosis >50% outcomes, a significant difference was found in the rate of restenosis between the CEA and CAS groups within 1 year (OR, 0.317; 95% CI, 0.228-0.441; P < 0.001) but not at 1.5 years (P = 0.301), 2 years (P = 0.686), or 5 years (P = 0.920). No nominally significant effects were demonstrated with respect to the cumulative incidence of occlusion (P = 0.195) or the cumulative incidence of restenosis for symptomatic patients (P = 0.170) between CEA and CAS., Conclusions: Although CAS was preferred over CEA, regardless of restenosis >50% or >70% after revascularization within 1 year, no significant difference was observed with extension of the follow-up period to >1 year. CAS was not associated with a greater cumulative incidence of occlusion or the cumulative incidence of restenosis for symptomatic patients., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The objectives of the present study were to investigate the effect of vitrification on the expression of the key genes associated with blastocyst developmental potential (β-catenin, E-cadherin, Oct-4, Cdx2, Gata3), and whether the presence of β-mercaptoethanol (β-ME, 100 μM) in in vitro culture (IVC) media will affect the expression of these genes. Buffalo pre-implantation embryos were divided into three groups: (1) fresh non-vitrified embryos were used as control, (2) vitrified embryos cultured with β-ME (+), and (3) vitrified embryos cultured without (-) β-ME. The results showed that all genes were affected by vitrification, however, the presence of β-ME in IVC media significantly (P < 0.05) modified the expression level of β-catenin, E-cadherin and Oct-4 in vitrified blastocyst compared to those cultured without β-ME. Protein expression analysis by immunofluorescence and western blot also revealed that the expression level of β-catenin and E-cadherin was significantly higher in vitrified embryos cultured with β-ME than those cultured without β-ME, which, in turn, was lower than fresh control group. However, there was no significant difference between vitrified groups in the expression level of Cdx2 and Gata3. Furthermore, the reduced rate of apoptosis in embryos cultured with β-ME confirms its role in protecting vitrified blastocyst against stress. In summary, vitrification alters the expression of the adhesion related genes in vitrified blastocyst, which may explain, at least in part, the reason for the low pregnancy rate following transfer of such embryos into recipient animal, and the supplementation of IVC media with β-ME significantly improved the quality of vitrified blastocyst evidenced by the modulation of the expression of blastocyst important genes, β-catenin, E-cadherin and Oct-4, and the ability to protect vitrified blastocyst against apoptosis., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The objectives of this study were to investigate the effect of buffalo oocyte-secreted factors (OSFs) on cumulus cells (CCs) functions, apoptosis and cGMP generation, and whether the direct contact between oocyte and CCs is essential for oocyte-mediated regulation of CCs functions. Buffalo CCs were cultured during IVM within three groups: (a) intact cumulus-oocyte complexes (COCs), (b) CCs cocultured with denuded oocytes (DOs) (CCs + DOs) and (c) CCs monolayer cultured alone (CCsM). After 24 hr of IVM, CCs were harvested for evaluation of the relative mRNA abundance of the genes encoding gap junction (GJA1), glycolysis (PFKP and LDHA), apoptosis (CASPASE-3 and BCL-2) and steroidogenesis (ER-β and PGR) by QRT-PCR, and CASPASE-3 proteins, using western blot. Intracellular cGMP content was also assessed by ELISA. Results showed that the relative abundance of LDHA, PFKP and BCL-2 significantly increased (p < 0.05) in COCs, whereas GJA1 and CASPASE-3 exhibited lower expression (p < 0.05) compared to CCs + DOs and CCsM groups. However, the expression levels of CASPASE-3, both mRNA and protein, were significantly (p < 0.05) downregulated in CCs + DOs compared to CCsM. There was no significant difference in the expression level of PGR and ER-β between the groups. The intracellular content of cGMP was notably (p < 0.05) higher in COCs compared to CCs + DOs and CCsM groups. In conclusion, this study demonstrated, for the first time, that buffalo OSFs protect CCs against apoptosis and stimulate their cGMP production; however, the regulation of cumulus glycolysis and gap junction is confined to those in close contact with the oocyte. Neither OSFs from COCs nor those from DOs have any effect on CCs steroidogenesis., (© 2018 Blackwell Verlag GmbH.)

The objectives of the present study were to evaluate the developmental competence of buffalo denuded oocytes (DOs) cocultured with cumulus cells (CCs) during in vitro maturation, and to investigate the mechanisms by which CCs promote oocyte maturation and development. Buffalo oocytes were matured in vitro for 24 h in three groups: (1) intact cumulus-oocyte complexes (COCs) (2) DOs cocultured with CCs (DOsCC), and (3) DOs cultured alone (DOs). Matured oocytes were used to determine the relative mRNA abundance of Gdf-9, Bmp15, Zar1, Caspase-3, Bcl-2, Zp2, Zp3, Cd9 and Pde3a by Rt-qPCR and CASPASE-3 protein expression by immunofluorescence. The intracellular content of cGMP, cAMP and MPF activity and the rate of embryonic development were also assessed. Results of the present study showed that in DOs, the relative mRNA abundance of Gdf-9, Bmp15, and Cd9 significantly (P < 0.05) decreased, whereas Caspase-3 (mRNA and protein levels), Bcl-2, and Pde3a exhibited higher expression than DOsCC and COCs. However, there was no significant difference among the groups in the expression level of Zar-1, Zp2, and Zp3. The intracellular content of cAMP and MPF activity was notably higher (P < 0.05) in DOs compared to COCs and DOsCC. There was no significant difference between COCs and DOsCC in cGMP content, which was significantly lower (P < 0.05) in DOs. Moreover, the cleavage and blastocyst rates were 58.4 ± 1.8%, 43.7 ± 1.1%, 18.4 ± 0.9% and 18.0 ± 1.3%, 11.0 ± 0.9% and 4.5 ± 0.6% in COCs, DOsCC and DOs groups, respectively. In conclusion, the presence of CCs protects buffalo DOs from apoptosis and promotes maturation through regulation of the intracellular content of cAMP and MPF activity and improves the fertilizing capacity of oocytes through modulation of the gamete fusion gene, Cd9., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Vegetation stoichiometry represents plant nutrition limitation status. Whether it can affect the species diversity of plant community remains to be explored. In this study, we examined plant carbon (C), nitrogen (N), phosphorus (P) concentrations and stoichiometry, and further analyzed the relationship between stoichiometry and species diversity in Artemisia ordosica community and Salix psammophila community in sand land of the Ningxia Habahu National Nature Reserve. The results showed that, for the S. psammophila community growing in mobile and semi-fixed sand dunes, there was a significant negative correlation between Simpson index and vegetation C/N ratio, but no significant correlation between Simpson index and vegetation N/P ratio. For A. ordosica community distributed in semi-fixed and fixed dunes, the Shannon index had a significant positive correlation with vegetation N/P ratio and a significant negative correlation with vegetation C/N ratio. Combined the vegetation stoichiometry with the results of regression analysis (RDA), P concentration and thus N/P ratio had different influences on the species diversity for A. ordosica community and S. psammophila community. Our results showed that vegetation stoichiometry has an important influence on species diversity of plant community in sand land.

Diversity and plasticity are the hallmarks of cells from the monocyte-macrophage lineage. Macrophages undergo classical M1 or alternative M2 activation in response to the microenvironment signals. Several transcription factors, such as peroxisome proliferator-activated receptors, signal transducers and activators of transcription, CCAAT-enhancer-binding proteins, interferon regulatory factors, Kruppel-like factors, GATA binding protein 3, nuclear transcription factor-κB, and c-MYC, were found to promote the expression of specific genes, which dictate the functional polarization of macrophages. Importantly, these transcription factors can be regulated by microRNAs (miRNAs), a group of small non-coding RNAs, which regulate gene expression through translation repression or mRNA degradation. Recent studies have also revealed that miRNAs control macrophage polarization by regulating transcription factors in response to the microenvironment signals. This review will summarize recent progress of miRNAs in the transcriptional regulation of macrophage polarization and provide the insights into the development of macrophage-centered diagnostic and therapeutic strategies.

Dextransucrase (DSR, EC2.4.5.1) from Leuconostoc mesenteroides 0326 which catalyzes sucrose to produce dextran, are popularly used in food and medicine industries. However, its poor kinetic stability especially at higher temperatures is a limiting factor for developing industrial applications. The aim of this study is to improve the enzyme activity and thermal stability of dextransucrase by single, double and triple mutations of proline and lysine. In this work, Pro-473, Pro-678, and Pro-856 were selected as engineering targets and individually replaced with serine. Lys-378, Lys-725, and Lys-955 were replaced with threonine, respectively. Mutant P473S/P856S (MW: 170kDa) was selected as the highest enzymatic activity mutant from fourteen mutants. Specifically, the mutant P473S/P856S showed a significant increase in thermal inactivation with a 7.4-fold increase in half-life at 35°C and a 2-fold increase in catalytic efficiency compared with the wild-type. The results of structural simulation are demonstrated that the new intramolecular hydrogen bonds in mutated enzymes increased structural stability, thereby increasing the thermal stability. The thermal stable mutants have an enormous application potential in food and pharmaceutical industry., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Reproductive capacity in animals and women declines with increasing age. Although ovarian aging is considered as a main cause for the decline of pregnancy rate, whether uterine aging occurs remains unclear. Even if blastocysts are transferred from young donors to older pseudopregnant recipients, the rate of implantation is still low, suggesting the occurrence of uterine aging. In this study, we compared the pregnancy rate and the uterine responsiveness of steroid hormones in ovariectomized mice at age between 2- and 12-month-old. Compared to 2-month-old mice, there is a significant decrease of both pregnancy rate and the number of implantation sites in 12-month-old mice. In ovariectomized mice, the uterine responsiveness of steroid hormones is also significantly different between 2- and 12-month-old mice. On day 4, Muc1 and PR level in 12-month-old mice is significantly higher than that in 2-month-old mice, while Hand2 level is significantly lower in 12-month-old mice. Our data suggest that the abnormal responsiveness of steroid hormones may contribute to the decline of pregnancy rate in 12-month-old mice., (Copyright © 2017 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)

Nanos2 belongs to the Nanos gene-coding family and is an important RNA-binding protein that has been shown to have essential roles in male germline stem cells development and self-renewal in mouse. However, little is known about Nanos2 in inchoate buffalo spermatogonia. Here, rapid-amplification of cDNA ends (RACE) was used to obtain the full-length buffalo Nanos2 sequence and bioinformatic analysis revealed a highly conserved Nanos2 sequence between buffalo and other mammalian species. Although Nanos2 was expressed in various tissues, the highest mRNA expression levels were found in testes tissue. Moreover, Nanos2 mRNA was abundant in fetal and pre-puberal testes but markedly decreased in the testes of adults. At the protein level, immunohistochemistry in pre-puberal testes revealed a pattern of NANOS2 expression similar to that for the undifferentiated type A spermatogonia marker PGP9.5. Furthermore, NANOS2 expression was low in adult testes and restricted to elongating spermatids. Altogether, our data suggest that Nanos2 is a potential preliminary molecular marker of inchoate buffalo spermatogonia, and may play an important role in buffalo spermatogonial stem cells (SSCs) development and self-renewal, as has been observed in other model animals., (Copyright © 2017. Published by Elsevier B.V.)

Purpose: Type I collagen is one of the most abundant components of extracellular matrix. We previously illustrated that murine fibrosarcoma L929 cells grew well on type I collagen gel and escaped from TNFα-induced cell death. In this study, we investigated the mechanism underlying the protective effect of collagen gel., Material and Methods: We used western blot, confocal microscopy, MTT assay and flow cytometry by introducing fluorescence staining to determine the expression levels of nuclear factor kappa B (NF-κB), inhibitory ratio and autophagy., Results: L929 cells on collagen gel showed higher expression of NF-κB in the nucleus. Inhibition of NF-κB with pyrrolidine dithiocarbamate hydrochloride (PDTC) or knockdown by NF-κB-siRNA canceled the protective effect of collagen gel on L929 cells from TNFα-induced death, suggesting for the role of NF-κB in the protection from cell death. We found a new aspect of the effect of PDTC on L929 cells cultured on collagen gel. PDTC alone without TNFα induced apoptosis in the L929 cells cultured on collagen gel but not the cells on plastic dish. The apoptosis induction of the L929 cells cultured on collagen gel with PDTC was repressed by inhibiting autophagy with chloroquine, an autophagy inhibitor, suggesting that autophagy contributes to the death induced by the treatment with PDTC. Possible underlying mechanism of this finding is discussed., Conclusion: NF-κB played an important role in protecting the L929 cells cultured on collagen gel from TNFα-induced death.

Object: MicroRNAs (miRNAs) play key roles in progression of cervical cancer. In the present study, we investigated the role of miR-214 in the process of migration, invasion and drug sensitivity to cisplatin in cervical cancer., Methods: We detected the differential expression of miR-214 in 19 cases cervical cancer tissues and normal tissues as well as 4 cervical cancer cells and one normal cervical cells by Real-time PCR. Then, wound healing assay, transwell invasion assay and MTT were used to detect the effects of migration, invasion and sensitivity to cisplatin of cervical cancer when miR-214 was overexpressed. Western blot, immunofluorescence and Flow Cytometry were used to detect the mechanism of migration, invasion and sensitivity to cisplatin. Next, bioinformatics analysis was used to find the target of miR-214. Through the luciferase reporter assay, Real-time PCR and western blot, we confirmed the binding relationship of miR-214 and FOXM1. In cervical cancer tissues, the expression of FOXM1 was detected by western blot and Immunohistochemistry. We also knocked down FOXM1 in cervical cancer cells, wound healing assay, transwell invasion assay and MTT were performed to detect the migration, invasion and sensitivity to cisplatin abilities of FOXM1. Western blot and Flow Cytometry were used to detect the mechanism of migration, invasion and sensitivity to cisplatin by FOXM1. Finally, we performed rescue expriments to confirm the function relationship between miR-214 and FOXM1., Results: 1. Our results showed that miR-214 was frequently downregulated in tumor tissues and cancer cells especially in CIN III and cervical cancer stages. 2. Overexpression of miR-214 significantly inhibited migration and invasion of cervical cancer cells and prompted the sensitivity to cisplatin. 3. FOXM1 was identified as a target of miR-214 and down-regulated by miR-214. 4. Knocking down FOXM1 could inhibited migration and invasion of cervical cancer cells and prompted the sensitivity to cisplatin. 5. FOXM1 was upregulated in tumor tissues. 6. The mechanism of migration, invasion and sensitivity to cisplatin were the resluts of changes of EMT and apoptosis. 7. The restoration of FOXM1 expression can counteract the effect of miR-214 on cell migration, invasion and sensitivity to cisplatin of cervical cancer cells., Conclusions: These findings indicate that miR-214 acts as a tumor suppressor during the process of migration, invasion and drug sensitivity through targeting FOXM1, suggesting miR-214 as a potential new diagnostic and therapeutic target for the treatment of cervical cancer., Competing Interests: None.

Dextrans with distinct molecular size and structure are increasingly being used in the food and pharmaceutical industries. Dextran is produced by dextransucrase (DSR, EC2.4.5.1), which is produced by Leuconostoc mesenteroides. DSR belongs to glycosyl hydrolase family (GH70) and synthesizes branched α-glucan (dextran) with both 5% α(1-3) and 95% α(1-6) glycosidic linkages. The DSR gene dex-YG (Genebank, Accession No. DQ345760) was cloned from the wild strain Leuconostoc mesenteroides 0326. This study generated a series of C-terminally truncated variants of dextransucrase and substituting the amino-acid residues in the active site of DSR. With shorter length of DSR, its polysaccharide-synthesizing capability was impaired heavily, whereas oligosaccharide (acting as prebiotics)-synthesizing capability increased significantly, efficiently producing special sizes of dextran. All truncated mutant enzymes were active. Results demonstrated that the catalytic domain dextransucrase was likely in 800 aa or less. Based on the three-dimensional structure model of dextransucrase built through homology modeling methods, the DSR and its mutants with the acceptor substrate of maltose and donor substrate of sucrose were studied by molecular-docking method. Substituting these amino-acid residues significantly affected enzyme activities. Compared with the wild-type dextran, mutant enzymes catalyzed the synthesis of a-glucan with 1-9% α(1-3) and 90-98% α(1-6) branching linkages. Some mutants introduced a small amount of α(1-4) linkages and α(1-2) linkages. This strategy can be effectively used for the rational protein design of dextransucrase., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Aims: The aim of this study was to examine the effect of alcohol on the decidualization of human endometrial stromal cells during early pregnancy., Methods: During in vitro decidualization, human endometrial stromal cells were treated with alcohol, 4-methylpyrazole hydrochloride (FPZ), the inhibitor of alcohol dehydrogenases (ADHs), and tetraethylthiuram disulfide (DSF), the inhibitor of acetaldehyde dehydrogenases (ALDHs), respectively. Cell viability and decidualization were examined. Apoptosis and proliferation were also evaluated., Results: The findings showed that ADHs and ALDHs were up-regulated during decidualization. After alcohol treatment, the cell viability of decidual stromal cells was significantly higher than control, which was abrogated by FPZ or DSF. When cells were treated with alcohol, proliferation-related signal pathways were up-regulated in decidualized cells. Additionally, FOXO1 transcriptionally up-regulates ADH1B., Conclusion: Our study provided an evidence that highly expressed ADHs and ALDHs endow decidual stromal cells an ability to alleviate the harm from alcohol., (© The Author 2016. Medical Council on Alcohol and Oxford University Press. All rights reserved)

Melatonin regulates broad aspects of plant responses to various biotic and abiotic stresses, but the upstream regulation of melatonin biosynthesis by these stresses remains largely unknown. Herein, we demonstrate that transcription factor heat-shock factor A1a (HsfA1a) conferred cadmium (Cd) tolerance to tomato plants, in part through its positive role in inducing melatonin biosynthesis under Cd stress. Analysis of leaf phenotype, chlorophyll content, and photosynthetic efficiency revealed that silencing of the HsfA1a gene decreased Cd tolerance, whereas its overexpression enhanced plant tolerance to Cd. HsfA1a-silenced plants exhibited reduced melatonin levels, and HsfA1a overexpression stimulated melatonin accumulation and the expression of the melatonin biosynthetic gene caffeic acid O-methyltransferase 1 (COMT1) under Cd stress. Both an in vitro electrophoretic mobility shift assay and in vivo chromatin immunoprecipitation coupled with qPCR analysis revealed that HsfA1a binds to the COMT1 gene promoter. Meanwhile, Cd stress induced the expression of heat-shock proteins (HSPs), which was compromised in HsfA1a-silenced plants and more robustly induced in HsfA1a-overexpressing plants under Cd stress. COMT1 silencing reduced HsfA1a-induced Cd tolerance and melatonin accumulation in HsfA1a-overexpressing plants. Additionally, the HsfA1a-induced expression of HSPs was partially compromised in COMT1-silenced wild-type or HsfA1a-overexpressing plants under Cd stress. These results demonstrate that HsfA1a confers Cd tolerance by activating transcription of the COMT1 gene and inducing accumulation of melatonin that partially upregulates expression of HSPs., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Both selenium (Se) and melatonin reduce cadmium (Cd) uptake and mitigate Cd toxicity in plants. However, the relationship between Se and melatonin in Cd detoxification remains unclear. In this study, we investigated the influence of three forms of Se (selenocysteine, sodium selenite, and sodium selenate) on the biosynthesis of melatonin and the tolerance against Cd in tomato plants. Pretreatment with different forms of Se significantly induced the biosynthesis of melatonin and its precursors (tryptophan, tryptamine, and serotonin); selenocysteine had the most marked effect on melatonin biosynthesis. Furthermore, Se and melatonin supplements significantly increased plant Cd tolerance as evidenced by decreased growth inhibition, photoinhibition, and electrolyte leakage (EL). Se-induced Cd tolerance was compromised in melatonin-deficient plants following tryptophan decarboxylase (TDC) gene silencing. Se treatment increased the levels of glutathione (GSH) and phytochelatins (PCs), as well as the expression of GSH and PC biosynthetic genes in nonsilenced plants, but the effects of Se were compromised in TDC-silenced plants under Cd stress. In addition, Se and melatonin supplements reduced Cd content in leaves of nonsilenced plants, but Se-induced reduction in Cd content was compromised in leaves of TDC-silenced plants. Taken together, our results indicate that melatonin is involved in Se-induced Cd tolerance via the regulation of Cd detoxification., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: Gelatin has been considered to exist as intermediate substance of collagen catabolism in tissue remodeling or under inflammatory conditions. We have initiated the study on possible biological functions of gelatin that can exist temporally and locally under the conditions of remodeling and inflammation Materials and methods: To this purpose, we investigated cell proliferation and survival on gelatin-coated dishes and the response to tumor necrosis factor α (TNFα)-induced cytotoxicity in L929 cells. Autophagy level, ATP level, and ROS generation are examined., Results: L929 cells detached from the gelatin-coated dishes and formed multicellular aggregates. TNFα-induced cytotoxicity in L929 cells was inhibited by gelatin-coating culture. The cells on gelatin-coated dishes showed reduced cellular ATP levels and increased adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) phosphorylation, leading to increased ROS generation and autophagy., Conclusion: This study showed that gelatin-coated culture protected L929 cells from TNFα-induced cytotoxicity and suggested for a possible pathophysiological function of gelatin in regulating cellular functions.

Serotonin (5-HT) modulates both neural and immune responses in vertebrates, but its role in insect immunity remains uncertain. We report that hemocytes in the caterpillar, Pieris rapae are able to synthesize 5-HT following activation by lipopolysaccharide. The inhibition of a serotonin-generating enzyme with either pharmacological blockade or RNAi knock-down impaired hemocyte phagocytosis. Biochemical and functional experiments showed that naive hemocytes primarily express 5-HT1B and 5-HT2B receptors. The blockade of 5-HT1B significantly reduced phagocytic ability; however, the blockade of 5-HT2B increased hemocyte phagocytosis. The 5-HT1B-null Drosophila melanogaster mutants showed higher mortality than controls when infected with bacteria, due to their decreased phagocytotic ability. Flies expressing 5-HT1B or 5-HT2B RNAi in hemocytes also showed similar sensitivity to infection. Combined, these data demonstrate that 5-HT mediates hemocyte phagocytosis through 5-HT1B and 5-HT2B receptors and serotonergic signaling performs critical modulatory functions in immune systems of animals separated by 500 million years of evolution.

Autophagy is a lysosome-mediated self-degradation process that mediates degradation and recycling of all major components of eukaryotic cells to maintain intracellular homeostasis. Autophagy is associated with leukemo-genesis, treatment, drug-resistance and recurrence of chronic myeloid leukemia (CML). Autophagy is a double-edged sword which has dual characteristics to promote survival and death of CML cells. Thus exploring different roles of autophagy under different conditions, finding out different autophagy pathways and combination with autophagy inducer or inhibitor of autophagy is of great importance to improve therapeutic effect, overcome drug-resistance and recurrence and finally come to a cure. This article makes a summary on the dual role of autophagy in CML.

Objective: Meta-analysis of the efficiencies of imatinib mesylate (IM) with or without interferon for chronic myeloid leukemia-chronic phase (CML-CP) patients., Methods: Published studies of IM with or without interferon for CML-CP patients as first-line therapy were collected from PubMed, Cochrane Central Register of Controlled Trials (CENTRAL) of the Cochrane Library, China National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), VIP information and WANFANG database. References of retrieved articles were also identified. The quality of each randomized controlled trial (RCT) was evaluated by the Cochrane collaboration's tool for assessing the risk of bias. Data analysis was performed with RevMan 5.1., Results: A total of 5 articles involving 1754 patients were included. Meta-analysis results showed that there were no statistical differences between IM with interferon and IM monotherapy for the complete cytogenetic response (CCyR) rate at 12 months,but IM with interferon could improve major molecular response (MMR) rate at 12 months (OR=1.57, 95% CI: 1.26-1.96, P=0.02). Furthermore, IM combined with pegylated-interferon demonstrated superiority for MMR at 12 months (OR=2.43, 95% CI: 1.78-3.33, P<0.01)., Conclusion: Combination of IM and interferon does not increase CCyR rate, but improve MMR rate at 12 months.