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This investigation aims to observe the effects of demodex infection and meibomian gland function in recurrent corneal erosion syndrome (RCES), as well as the efficacy of intense pulsed light (IPL) in treating RCES. The study enrolled thirty patients diagnosed with RCES (30 eyes) alongside a control group of thirty-one individuals (31 eyes). Both cohorts underwent a series of diagnostic evaluations, including eyelash sampling, Demodex mite enumeration, infrared imaging of the meibomian glands, and blepharolipin scoring. The RCES subjects were further categorized into two subgroups upon stabilization for comparative analysis of treatment outcomes: the RCES-A subgroup received IPL therapy (16 patients), and the RCES-B subgroup was administered medication treatment (14 patients). Post-treatment, all participants were re-evaluated using the initial diagnostic procedures to monitor for recurrence. Preliminary findings indicated significant differences between the RCES and control groups in terms of meibomian gland scores (4 [3.0, 4.0] vs. 2 [1.0, 3.0]), blepharolipin scores (15.5 [11.0, 16.8] vs. 8.0 [5.5, 10.0]), and lid margin scores (3.0 [2.8, 3.0] vs. 2.0 [1.0, 3.0]), with P < 0.01 for all comparisons. Additionally, the Demodex count was significantly higher in the RCES group (8.0 [4.0,9.0]) compared to the control (0 [0, 2]) (Z = - 4.13, P = 0.00), with a Demodex positivity rate of 83.3% in the RCES group versus 38.7% in the control group (χ2 = 7.60, P < 0.01). Post-treatment, the RCES-A subgroup exhibited significant improvements in meibomian gland loss scores, blepharolipin scores, lid margin abnormality scores, and a reduction in Demodex counts (P < 0.01), with a post-treatment Demodex positivity rate of 56.3% (P = 0.11). During the follow-up, the RCES-A subgroup experienced a lower relapse rate compared to the RCES-B subgroup (1 vs. 6 patients). The findings suggest a correlation between meibomian gland dysfunction and Demodex infestation with the incidence of RCES. The application of IPL therapy in combination with meibomian gland massage demonstrates significant potential in enhancing meibomian gland functionality, reducing Demodex counts, and effectively mitigating the recurrence of RCES. Clinical trial registration: https://www.chictr.org.cn/ ChiCTR2000039494 (30/10/2020)., (© 2024. The Author(s).)

Despite significant advances in assisted reproductive technology (ART), recurrent implantation failure (RIF) still occurs in some patients. Poor endometrial receptivity and abnormal human endometrial stromal cell (HESC) proliferation and decidualization have been identified as the major causes. Ubiquitin-specific protease 22 (USP22) has been reported to participate in the decidualization of endometrial stromal cells in mice. However, the role of USP22 in HESC function and RIF development remains unknown. In this study, clinical endometrial tissue samples were gathered to investigate the involvement of USP22 in RIF, and HESCs were utilized to examine the molecular mechanisms of USP22 and Forkhead box M1 (FoxM1). The findings indicated a high expression of USP22 in the secretory phase of the endometrium. Knockdown of USP22 led to a notable reduction in the proliferation and decidualization of HESCs, along with a decrease in FoxM1 expression, while overexpression of USP22 yielded opposite results. Furthermore, USP22 was found to deubiquitinate FoxM1 in HESCs. Moreover, both USP22 and FoxM1 were downregulated in the endometria of patients with RIF. In conclusion, these results suggest that USP22 may have a significant impact on HESCs proliferation and decidualization through its interaction with FoxM1, potentially contributing to the underlying mechanisms of RIF pathogenesis., Competing Interests: Declaration of competing interest The authors declare they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Recurrent spontaneous abortion (RSA) is a complex pathological process involving diverse factors, in which the dysregulated functions of trophoblasts cannot be ignored. Long noncoding RNA (lncRNA) has been reported to play a significant role in regulating the functions of trophoblasts in RSA. However, the impact and potential mechanism of lncRNA small nucleolar RNA host gene 12 (lncSNHG12) remain unclear. The role of lncSNHG12 in RSA was investigated through in vivo experiments and clinical samples. Co-IP and RNA pull down were conducted to explore the molecular mechanisms in trophoblasts. Our results showed that lncSNHG12 promoted the migration and invasion of trophoblasts by interacting with Iodothyronine deiodinase 2 (Dio2), which regulating the EMT process of trophoblasts by interacting with Snail. Moreover, in vivo experiments confirmed that lncSNHG12 could improve the fetal absorption rate of the abortion mice. The clinical samples revealed that lncSNHG12, Dio2 and Snail were down-regulated in the villous tissues of RSA patients, and positive correlations were confirmed between lncSNHG12 and Dio2, as well as Dio2 and Snail. In summary, the lncSNHG12/Dio2/Snail axis might be involved in the development of RSA by regulating the invasion and migration of trophoblasts. Abbreviations: RSA, recurrent spontaneous abortion; EVTs, extravillous trophoblasts; EMT, epithelial-to-mesenchymal transition; lncRNA, long non-coding RNA; Dio2, iodothyronine deiodinase 2; SNHGs, small nuclear RNA host genes; snoRNAs, small nuclear cell RNAs; LPS, lipopolysaccharide; De, derived decidua; Jz, junctional zone; Lz, labyrinth zones; RIP, RNA Binding Protein Immunoprecipitation; Co-IP, Co-Immunoprecipitation; RPISeq, RNA-Protein Interaction Prediction., 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 Elsevier Inc. All rights reserved.)

The present study examined the pharmacokinetics of IMM-H012 in rat plasma, utilizing ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Internal standard cilostazol was employed, and plasma samples were processed using acetonitrile precipitation. A mobile phase (acetonitrile-0.1% formic acid in water) with gradient elution was used to achieve chromatographic separation using a UPLC BEH C18 column. In multiple reaction monitoring mode, electrospray ionization MS/MS was utilized in positive ionization mode. Based on findings, the lower limit of quantification was 2 ng/mL, and the linearity of IMM-H012 in rat plasma was found to be acceptable within the range of 2-2000 ng/mL (R 2  > 0.995). The intra-day and inter-day precision relative standard deviation was less than 14% of IMM-H012 in rat plasma. The matrix effect was within the range of 102%-107%, and the accuracy ranged from 92% to 113%. Pharmacokinetics of IMM-H012 in rats after oral administration were successfully studied using UPLC-MS/MS., (© 2024 John Wiley & Sons Ltd.)

Background: To observe whether the effect of orthokeratology (OK) lenses on myopia control in children with allergic conjunctivitis (AC) after three years of wear differs from that in children without allergic conjunctivitis (nAC) and to identify the potential influencing factors., Methods: This was a retrospective case-control study. Patients aged 8-15 years who were fitted with OK lenses in 2019 were collected. A three-year follow-up was also conducted, documenting all corneal adverse events (AEs) and the increase in axial length (AL) of the eye after three years of wearing OK lenses. Patients were divided into groups with and without AC based on their medical history and physical signs at the initial fitting. Baseline data and AL elongation after three years were compared between the two groups., Results: A total of 309 patients were included in this study, with 47 in the AC group and 262 in the nAC group. There were no statistically significant differences between the two groups in terms of age, sex, spherical equivalent (SE), AL of the eye and environment. After three years of OK lens wear, the AL elongation in the AC group was 0.96 ± 0.45 mm, whereas it was 0.69 ± 0.45 mm in the nAC group (P < 0.001). The extent of AL elongation in AC patients was significantly greater than that in nAC patients. During the three-year follow-up period, the duration of OK lenses discontinuation due to corneal AEs in the AC group was greater than that in the nAC group (P < 0.05)., Conclusions: This study found that allergic conjunctivitis can affect the efficacy of OK lenses in controlling myopia after three years of treatment., 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. Published by Elsevier Ltd.)

Unexplained recurrent spontaneous abortion (URSA) is a serious reproductive issue that affects women of childbearing age. Studies have shown a close association between disrupted circadian rhythm and impaired epithelial-mesenchymal transition (EMT) in trophoblasts during URSA, although the underlying mechanism is not known. The current study investigated the regulatory relationship between circadian rhythm gene cryptochrome 2 (CRY2) and ferroptosis on the migratory ability of trophoblast cells. Cell proliferation experiments, wound-healing assays, and expression of related markers were conducted to study EMT. Trophoblastic ferroptosis was confirmed by the expressions of malondialdehyde, glutathione, mitochondrial membrane potential, divalent iron ions, and related genes. The results showed significant increased expression of CRY2 and decreased expression of brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein 1 (BMAL1) in the URSA villous tissues, accompanied by iron-dependent oxidative changes and abnormal expression of ferroptosis-related proteins. CRY2 and BMAL1 were co-localized and functioned as a feedback loop, which regulated the dynamic changes of EMT-related markers in trophoblast cells. CRY2 promoted trophoblastic ferroptosis, whereas BMAL1 had the opposite effect. Particularly, the ferroptosis inhibitor (ferrostatin-1) effectively reversed the trophoblastic ferroptosis and EMT inhibition caused by CRY2 overexpression. Collectively, these results suggest that CRY2 regulates trophoblastic ferroptosis and hinders cellular EMT and migratory ability by suppressing BMAL1 expression., (Copyright © 2024 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

The ideal tissue engineering scaffold should facilitate rapid cell infiltration and provide an optimal immune microenvironment during interactions with the host. Electrospinning can produce two-dimensional (2D) membranes mimicking the extracellular matrix. However, their dense structure hinders cell penetration, and their thin form restricts scaffold utility. In this study, latticed hydrogels were three-dimensional (3D) printed onto electrospun membranes. This technique allowed for layer-by-layer assembly of the membranes into 3D scaffolds, which maintained their resilience impressively under both dry and wet conditions. We assessed the cellular and host responses of these 3D nanofiber scaffolds by comparing random membranes and mesh-like membranes with three different mesh sizes (250, 500, and 750 μm). It was found that scaffolds with a mesh size of 500 μm were superior for M2 macrophage phenotype polarization, vascularization, and matrix deposition. Furthermore, it was confirmed by subsequent experiments such as RNA sequencing that the mesh-like topology may promote polarization to the M2 phenotype by affecting the PI3K/AKT pathway. In conclusion, our work offers a novel method for transforming 2D nanofiber membranes into 3D scaffolds. This method boasts flexibility, allowing for the use of varied electrospun membranes and hydrogels in terms of structure and composition. It has vast potential in tissue repair and regeneration., (© 2024. The Author(s).)

In order to promote the sustainable economic development, it is critical employ the digital economy to solve the mismatch dilemma of land and marine factors in coastal areas. It analyzed the influencing mechanisms between the digital economy, land and labor factor mismatch and coastal economic sustainable development using network development and new economic growth theories. The intermediary and regulating effect models were used for empirical tests using panel data from 11 Chinese coastal provinces (city or district) between 2009 and 2018. Results found that: (1) Digital economy promoted the sustainable development of land and marine binary economies in coastal areas; (2) Digital economy improved the factor mismatch of land and marine binary economies, which further affected the sustainable economic development; (3) Market integration is conducive to alleviating land and marine factor mismatch and strengthening the optimization effect of the digital economy on the factor mismatch. This research provides a new perspective for clarifying the mechanism of the digital economy on sustainable economic development, as well as a reference for the realization of rational allocation of factor resources and sustainable economic development by taking factor mismatch of land and marine binary economies and market integration as the intermediary variables and regulatory variables., Competing Interests: Wu ShuJuan reports financial support was provided by 10.13039/501100007310Wuyi University. Tang JianHua reports a relationship with Wuyi University that includes: board membership., (© 2024 The Authors. Published by Elsevier Ltd.)

During embryo implantation, trophoblast cells rely on large amounts of energy produced by glycolysis for their rapid growth and invasion. The disorder of trophoblast metabolism may lead to recurrent spontaneous abortion (RSA). Lactate, which is produced by the glycolysis of trophoblast cells during early pregnancy, can promote the polarization of M2 macrophages and maintain an anti-inflammatory environment at the maternal-fetal interface. Our study found that amine oxidase copper-containing 4 pseudogene (AOC4P) was abnormally increased in villi from RSA patients. It inhibited the glycolysis of trophoblast cells and thus hindered the polarization of M2 macrophages. Further studies showed that AOC4P combines with tumor necrosis factor receptor-associated factor 6 (TRAF6) to upregulate TRAF6 expression. TRAF6 acted as an E3 ubiquitin ligase to promote ubiquitination and degradation of zeste homolog 2 (EZH2). These results provided new insights into the important role played by AOC4P at the maternal-fetal interface., 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.)

Salidroside shows an inhibitory effect on myocardial ischemia/reperfusion (I/R) injury; however, the underlying mechanism remains to be explored. The present work analyzes the mechanism that drives salidroside to ameliorate I/R-induced human cardiomyocyte injury. Human cardiomyocytes were subjected to I/R treatment to simulate a myocardial infarction cell model. Cell viability, cell proliferation, and cell apoptosis were analyzed by CCK-8 assay, EdU assay, and flow cytometry analysis, respectively. RNA expression levels of circ&#95;0097682, miR-671-5p, and F-box and ubiquitin-specific peptidase 46 (USP46) were detected by qRT-PCR. Protein expression was measured by Western blotting assay. The levels of IL-6, IL-1β, and TNF-α in cell supernatant were detected by enzyme-linked immunosorbent assays. Salidroside treatment relieved I/R-induced inhibitory effect on AC16 cell proliferation and promoting effects on cell apoptosis, inflammation, and oxidative stress. Salidroside inhibited circ&#95;0097682 expression in I/R-treated AC16 cells. Salidroside-mediated inhibition of I/R-induced cell injury involved the downregulation of circ&#95;0097682 expression. In addition, circ&#95;0097682 bound to miR-671-5p in AC16 cells, and miR-671-5p inhibitors rescued salidroside pretreatment-mediated effects in I/R-treated AC16 cells. Moreover, miR-671-5p targeted USP46 in AC16 cells, and USP46 introduction partially relieved circ&#95;0097682 depletion or salidroside pretreatment-induced effects in I/R-treated AC16 cells. Salidroside ameliorated I/R-induced AC16 cell injury by inhibiting the circ&#95;0097682/miR-671-5p/USP46 pathway., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aplastic anemia (AA) is a T cell immune mediated autoimmune disease in which cytokines, particularly IFN-γ are pathogenesis factors. Glucose metabolism is closely related to effector functions of activated T cells, such as IFN-γ production. The characteristics of glucose metabolism and whether interfering with glucose metabolism could affect T cells produce IFN-γ ability in AA patients remains unknown. In this study, we examined the characteristics of glucose metabolism in T cells from AA patients and the effects of the glucose metabolism inhibitor 2-deoxy-D-glucose (2-DG) on the ability of T cell production IFN-γ. Our data demonstrated abnormal glucose metabolism in stimulated T cells from AA patients, mainly reflected by increased glucose uptake and lactate secretion. In addition, EM and T EMRA cells exhibit higher glucose uptake in patients with AA compared with healthy individuals. Moreover, the frequency of IFN-γ + was reduced by 2-DG in T cell from AA patients. Unexpectedly, 2-DG re-normalized the frequency of IFN-γ + in other T cell subsets, except for in the T EMRA . In conclusion, our study reveals for the first time the existence of enhanced aerobic glycolysis in T cells from AA patients, and different T cell subsets exhibit different extent glucose uptake requirements. Aerobic glycolysis regulation may be a potential therapeutic strategy for aberrant T cell immunity. Moreover, T EMRA may have specific metabolic abnormalities, which should receive more attention in future targeted immune metabolism research.

Aberrant polarization and functions of decidual macrophages are closely related to recurrent spontaneous abortion (RSA). C1q/tumor necrosis factor-related protein 6 (CTRP6) is a member of the adiponectin paralog family, and plays indispensable roles in inflammation, glucose uptake and tumor metastasis. However, the regulatory effect of CTRP6 on macrophage polarization and glycolysis in RSA and the underlying mechanisms have not been fully elucidated. In the present study, we first found that CTRP6 expression was positively correlated with the M1 macrophage marker (CD86) in decidual tissues by dual immunofluorescence analysis. In vitro experiments indicated that CTRP6 could facilitate M1 macrophage activation through the PPAR-γ/NF-κB pathway and manipulate the glycolysis of macrophages. Notably, in addition to silencing CTRP6, treatment with a PPAR-γ agonist (GW1929) inhibited M1 macrophage polarization and rescued embryo absorption in vivo. Taken together, these results identify previously unrevealed functions of CTRP6 in macrophage transformation during RSA., 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.)

Background: Polycystic ovary syndrome (PCOS) is a multifactorial endocrine disease, which is an important cause of female infertility worldwide. PCOS patients are in a state of chronic low-grade inflammation, and immune imbalance is considered as a potential cause of its pathogenesis., Methods: The expression of AOC4P in PCOS and normal ovarian granulosa cells (GCs) was detected by real-time quantitative PCR. KGN cells were induced by dihydrotestosterone at 500 ng/mL to construct the PCOS model. After lentivirus-infected, KGN cells were constructed with AOC4P overexpression cell lines, the proliferation and apoptosis levels of KGN cells in AOC4P and NC groups were detected. Human monocyte cell line (THP-1)-derived macrophages and peripheral blood mononuclear cells (PBMC) were co-cultured with KGN cells for 48 h, respectively, and the differentiation of macrophages and CD4+ T cells were detected by flow cytometry., Results: Decreased AOC4P expression was found in PCOS patients. After constructing the PCOS cell model, we observed that overexpression of AOC4P promoted KGN cell proliferation and inhibited apoptosis. After co-culture with AOC4P overexpressed KGN cells, M1 macrophages decreased, M2 macrophages increased, T helper cells type 1 (Th1)/Th2 ratio increased, and regulatory T cell (Treg) cells increased. Finally, we found that AOC4P inhibited the activation of the nuclear factor κ B (NF-κB) pathway in KGN cells., Conclusions: In this study, we found that AOC4P regulated the NF-κB signaling pathway by inhibiting the phosphorylation of P65, thereby affecting the proliferation and apoptosis of GCs, altering the differentiation of macrophages and T cells, thus contributing to the pathogenesis of PCOS., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Trophoblasts are significant components of the placenta and play crucial roles in maternal-fetal crosstalk. Adequate trophoblast migration and invasion are essential for embryo implantation and healthy pregnancy. Ubiquitin-specific protease 7 (USP7), a member of the deubiquitinating enzyme family, regulates the processes of migration and invasion in multiple tumor cells. However, the effects of USP7 on trophoblasts and its possible mechanism in the development of recurrent spontaneous abortion (RSA) are still unclear. In this study, we analyzed the expression of USP7 in villous tissues obtained from RSA patients and healthy controls, and then GNE-6776 (a USP7-specific inhibitor) and USP7 siRNA were used in a trophoblast cell line, HTR-8/SVneo, to further assess the effect of USP7 on the biological function of trophoblasts. Our results provide convincing evidence that USP7 is downregulated in the placental villous tissues of RSA patients. USP7 was found to have a crucial role in the proliferation, apoptosis, migration, invasion, and epithelial-mesenchymal transition (EMT) process of trophoblast cells. Further experiments revealed that USP7 directly interacted with the enhancer of zeste homolog 2 (EZH2) and regulated the Wnt/β-catenin signaling pathway in trophoblasts. Taken together, these findings indicate the vital role of USP7 in regulating trophoblast proliferation, migration and invasion, thus affecting the pathogenesis of RSA, providing new insights into the important role of USP7 in the maternal-fetal interface., (© The Author(s) 2023. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Rationale: Corneal opacity can be caused by various disease. Generally, the opacity gradually increases as the disease progresses. Sudden corneal opacity is mainly caused by corneal trauma, toxic drugs entering the cornea, or acute edema of the keratoconus. However, sudden corneal opacity caused by diabetes has not been reported., Patient Concerns: A 60-year-old man reported blurred vision and the black eye became white in appearance in the left eye for 5 days. The patient had a history of diabetes which had not been treated., Diagnoses: He underwent slit-lamp examination, anterior segment optical coherence tomography, ultrasound bio microscopy, B-mode ultrasound, corneal endothelial examination, random blood glucose testing, and other examinations. The diagnosis of Diabetic Keratopathy was made., Interventions: Topical glucocorticoids and dilating eye drops were administered and undergo blood sugar control treatment., Outcomes: The corneal of the patient was completely transparent in a few days, and the flocculent exudation in the anterior chamber disappeared., Lessons: Although diabetes generally causes chronic corneal edema, acute corneal edema may also occur when blood sugar is poorly controlled. Therefore, when we see sudden corneal opacity without obvious incentives, we must consider systemic diseases, especially diabetes., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

A theoretical mechanism was analyzed from the micro perspective of the enterprise to explore how information accessibility moderates the effect of accounting manipulation on the sustainable development of digital enterprises. Using data from 1200 listing digital enterprises in China and the DEA-Malmquist index method, the efficiency value of digital enterprises in 2007-2021 was estimated to represent the index of sustainable development of digital enterprises. The accounting manipulation was detected using the panel PSM-DID method based on the Administrative Measures for the Recognition of High-tech Enterprise's policy. The information accessibility value was estimated based on the MDA method. Empirical studies were conducted using text analysis, the panel PSM-DID method, and the double moderating effect model. The results showed that: (1) Accounting manipulation had a negative impact on the sustainable development of "true" digital enterprises and the "fake" digital enterprises. (2) Information accessibility directly and positively enhanced the technological progress and scale efficiency of digital enterprises, and its moderating effect was heterogeneous, with a significant moderating effect on the "true" digital enterprises and a negative effect on the "fake" ones., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Wu 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.)

Tetrahydrobiopterin (BH4) is a vital coenzyme for several enzymes involved in diverse enzymatic reactions in animals. BH4 deficiency can lead to metabolic and neurological disorders due to dysfunction in its metabolism. Sepiapterin reductase (SPR) and dihydrofolate reductase (DHFR) are crucial enzymes in the BH4 de novo synthesis pathway and salvage pathway, respectively. Dihydrobiopterin (BH2) is an oxidized product of BH4 metabolism. The ratio of BH4/BH2 is a key indicator of the stability of BH4 levels. The de novo pathway of BH4 synthesis is well-defined; however, little is known about the mechanisms of the salvage pathway in insects. Herein, we used the natural BmSPR mutant silkworm (lem) as a resource material. Our results reveal that the BmDHFR expression and the BH4/BH2 ratio were remarkably higher in lem as compared to the wild-type silkworm. In BmN cells, knockdown of BmSpr showed increased BmDHFR expression, while the BH4/BH2 ratio decreased after BmDhfr knockdown by RNAi. Furthermore, simultaneous RNAi of BmSpr and BmDhfr showed a further decrease in the BH4/BH2 ratio. These manifest that the expression of BmDHFR is up-regulated to trigger an increase in the BH4/BH2 ratio when the de novo synthesis of BH4 is blocked in silkworm. Additionally, the knockdown of BmSpr in wild-type silkworms also showed an increased BmDHFR level and BH4/BH2 ratio. Taken together, when the silkworm BH4 de novo synthesis pathway is blocked, the salvage pathway is activated, and BmDHFR plays an important role in maintaining the metabolic balance of silkworm BH4. This study enriches our understanding of the molecular mechanism of the BH4 salvage pathway and lays a good foundation for further studies on BH4 using the silkworm as a model insect., 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 © 2022 Elsevier B.V. All rights reserved.)

Macrophages are known to be pivotal for ensuring the establishment of the immune tolerance microenvironment at the maternal-fetal interface. In particular, trophoblasts stay in close contact with decidual macrophages (DMs), which have been reported to play an active role in the modulation of the polarization of DMs. Thus, any dysfunction of trophoblasts might be associated with certain pregnancy-related complications, such as recurrent spontaneous abortion (RSA). Enhancer of zeste homolog 2 (EZH2) is an important epigenetic regulatory gene that has been previously shown to be related to immune regulation. The present study assessed the expression of EZH2 in villi tissue obtained from healthy controls and RSA patients. Trophoblasts conditioned medium was collected to incubate macrophages differentiated from the THP-1 cell line. The expression and function of EZH2 in trophoblasts were knocked down either by the use of siRNA or GSK126 as an inhibitor. Our results show a significant decrease in the expression of EZH2 in villi tissue from RSA patients as compared to healthy controls. Further, the inhibition of expression or function of EZH2 in trophoblasts promoted M1 macrophage polarization, which might be involved in the pathogenesis of RSA. Moreover, the suppression of EZH2 was found to affect the secretion of immune and inflammatory cytokines in trophoblasts. Altogether, these results indicated the importance of EZH2 in the regulation of immune functions of trophoblasts and thus highlighted its potential to be explored as a therapeutic target to prevent and treat pregnancy loss., (© 2021. The Author(s).)

It has been reported that oxidative stress and chronic inflammation may be involved in the pathogenesis of polycystic ovary syndrome (PCOS). 8-oxoguanine DNA glycosylase (OGG1) is the main glycosylase that catalyzes the excision of DNA oxidation products. In this study, we investigated the role and potential mechanisms of OGG1 in the development of PCOS. We first analyzed OGG1 levels in serum and follicular fluid (FF) of PCOS patients, and significantly elevated OGG1 levels were noted in PCOS patients. We similarly observed a significant upregulation of OGG1 expression levels in ovarian tissue of the dehydroepiandrosterone (DHEA)-induced PCOS rat model. In addition, increased apoptosis and increased production of reactive oxygen species (ROS) were observed after the addition of OGG1-specific inhibitor (TH5487) in human granulosa-like tumor cell line (KGN) cells following a concentration gradient, along with a significant decrease in mRNA levels of inflammatory factors such as CXCL2, IL-6, MCP1, IL-1β, and IL-18. Significant decreases in protein phosphorylation levels of P65 and IκBα were also observed in cells. In addition, we found a significant positive correlation between OGG1 and IL-6 expression levels in human and DHEA-induced PCOS rat models. In conclusion, our results suggest that OGG1 might be involved in the pathogenesis of PCOS by regulating the secretion of IL-6 through NF-κB signaling pathway, and there might be a balance between the inhibition of oxidative stress and the promotion of chronic inflammation by OGG1 on KGN cells., (Copyright © 2022 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier B.V. All rights reserved.)

The purpose of this study was to determine the regulation of the miR-410-5p /ITGA6 axis on the biological functions of trophoblast cells and the mechanism involved in recurrent spontaneous abortion（RSA）. We used qRT-PCR and Western blotting to quantify the expression levels of Mir-410-5p and ITGA6 in placenta of RSA and normal, and found that compared with normal placenta, the placenta of RSA patients showed higher miR-410-5p and lower ITGA6 expression. Dual luciferase reporter gene assay confirmed the binding of miR-410-5p to ITGA6. The expression of miR-410-5p and ITGA6, and proliferation, apoptosis, invasion and migration of trophoblast cells and the effect on the polarization of M2 macrophages were detected in the trophoblast derived cell lines HTR8/Svneo transfected with miR-410-5p mimic, sh-miR-410-5p and si-ITGA6 respectively. Meanwhile, the molecular mechanism of ITGA6 regulation on trophoblast cells was explored. Transfection with miR-410-5p mimic or si-ITGA6 attenuated the proliferation, migration and invasion and induced apoptosis of HTR-8/SVneo cells. Transfection of sh-miR-410-5p promoted proliferation, migration and invasion, and weakened apoptosis of HTR-8/SVneo cells. In addition, overexpression of miR-410-5p in trophoblast cells inhibited the polarization of M2 macrophages, while knockdown of miR-410-5p was beneficial to recruitment of trophoblast cell and promoted the polarization of M2 macrophages. ITGA6 may affect the biological functions of trophoblast cells by regulating PI3K/AKT and MAPK signaling pathways. In conclusion, miR-410-5p mediates trophoblast cell proliferation, apoptosis, invasion and migration through regulating ITGA6 expression., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Covalent organic frameworks (COFs) have recently gained rising consideration for visible light photocatalysis. Their property could be accurately established with specific reactions in which the most investigated one turns out to be the aerobic oxidation of amines. In this contribution, a hydrazone-linked 2D (two-dimensional) porphyrinic COF, Por-DETH-COF, was assembled from 5,10,15,20-tetrakis(4-benzaldehyde)porphyrin (p-Por-CHO) and 2,5-diethoxyterephthalohydrazide (DETH) and its photocatalytic activity was duly appraised with the aerobic oxidation of amines. Thereby, the red light-driven selective oxidation of benzyl amines to imines was obtained in very high conversions and selectivities with ambient air as the oxidant. Importantly, the photocatalytic system exhibited remarkable compatibility of functional groups and extensive scope of benzyl amines. Notably, the Por-DETH-COF photocatalyst displayed outstanding recyclability after five successive cycles. This work suggests that 2D COFs could contribute a unique juncture for selective organic transformations by photocatalysis., 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 © 2021 Elsevier Inc. All rights reserved.)

Food-derived hypotensive peptides have attracted attention in the field of active peptide research in recent years. In this study, based on ACE inhibition rate and using the Box-Behnken central combination design principle to optimise the process of ACE inhibitor peptides prepared by double-enzyme hydrolysis. The amino acid sequences of ACE inhibitor peptides were determined by liquid chromatography mass spectrometry (LC-MS/MS), and their binding to ACE was studied by molecular docking. The optimal processing conditions were 1:1 alkaline protease: compound protease, pH was 8.43, enzymolysis temperature was 44.32 °C, and enzymolysis time was 3.52 h. Under these conditions, the ACE inhibition rate reached 65.12%, and the inhibition rate after separation and purification was 80.68% (IC 50 = 0.9 mg/mL). Three novel peptides with ACE inhibitory activity were detected by LC-MS/MS, with sequences LVYP (Leu-Val-Tyr-Pro), VYPW(Val-Tyr-Pro-Trp) and YPWT(Tyr-Pro-Trp-Thr). Molecular docking revealed that the three novel peptides all established hydrogen bonds with the S1(Tyr523, Glu384, Ala354) and S2 (His353) pockets of ACE. Among them, LVYP, VYPW and YPWT, respectively, formed eleven hydrogen bonds, six hydrogen bonds and nine hydrogen bonds with ACE. The study revealed that these peptides have the potential for the development of novel ACE inhibitor drugs and provide a new avenue for high-value utilisation of mushrooms scraps.

Soil phosphate (Pi) deficiency is a global issue and a major constraint on plant growth. Plants typically acclimatize to low Pi by enhancing their P utilization and/or P acquisition efficiencies; however, different species have variable preferred strategies. RNA sequencing analysis was performed on the shoots and roots of Zygophyllum xanthoxylum , under 1 day and 10 days of Pi stress, to investigate their adaptation strategies to P deprivation. A total of 364,614 unigenes and 9,270 differentially expressed genes (DEGs) were obtained via transcriptome sequencing. An analysis of the DEGs revealed that under the 10D treatment, anthocyanin synthesis genes were upregulated under Pi stress, whereas gibberellin, ethylene, and cytokinins synthesis genes were upregulated, and abscisic acid synthesis genes were downregulated. Genes related to organic acid synthesis, encoding for purple acid phosphatases (APase) and nucleases (RNase) were upregulated under the 1D and 10D treatments, respectively. Furthermore, genes associated with Pi transport were induced by Pi stress. Zygophyllum xanthoxylum has special P adaptation strategies, the variation trends of genes involved in external P mobilization and acquisition, which were different from that of most other species; however, the expression levels of organophosphorus mobilization related genes, such as APases and RNases, were significantly increased. Meanwhile, PHT2s and TPTs, which distributed Pi to effective sites (e.g., chloroplast), played critical roles in the maintenance of photosynthesis. We speculated that these were economic and energy saving strategies, and there are critical adaptive mechanisms that Z. xanthoxylum employs to cope with deficits in Pi., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hu, Zhang, Niu, Nan, Wu, Gao and Fu.)

This work reported two monolithic conjugated microporous polymer (CMP) foams synthesized through the Sonogashira-Hagihara cross-coupling reaction without mechanical stirring. The as-synthesized (CMP-ED and CMP-PT) foams exhibited superior hydrophobicity and low apparent density of 58 mg cm -3 and 63 mg cm -3 . In addition, CMP-ED displayed a low thermal conductivity of 34.04 mW m -1 K -1 , which was comparable with commercial SiO 2 aerogels (34.09 mW m -1 K -1 ) at 50% humidity conditions. When the environment humidity was raised from 50% to 70%, the thermal conductivity of CMP-ED and commercial SiO 2 aerogels improved by 0.12% and 7%, respectively. Furthermore, XRD, FTIR, BET and TG were conducted to evaluate the bulk structure and stability of CMP-ED and CMP-PT. The results illustrated the thermal conductivity values were greatly affected by the pore structure of foams. And the strong hydrophobicity and the narrow pore structure were responsible for the good thermal insulation performance under humid conditions. Considering the low density, superhydrophobicity, excellent physicochemical stability and impervious thermal conductivity in a high humidity environment, this CMP-ED presented great potential as an insulating material in a humid environment., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The development of functional materials with better flame-retardant and thermal insulation properties has attracted considerable attention for energy storage applications in modern society. Here, we describe a facile approach for the preparation of conjugated microporous polymer hollow spheres (CMP-HSs) by using SiO 2 nanoparticles as a template via the Sonogashira-Hagihara cross-coupling reaction. The as-synthesized CMP-HSs have good thermal stability with a thermal decomposition temperature of up to 281 °C, high porosity (the BET specific surface area is measured to be approximately 666 m 2 g -1 ) along with lipophilic and hydrophobic characteristics. To further improve their flame retardancy, CMP-HSs were treated with dimethyl phosphonate (DMMP) though an immersion method to prepare the CMP-HSs composite (CMP-HSs-DMMP) flame-retardants. By introducing CMP-HSs-DMMP into the epoxy resin (EP) matrix, the as-prepared EP composites showed excellent flame-retardant properties, e.g., the peak heat release rate (pHRR) and total heat release (THR) value of EP composites containing only 0.2% CMP-HSs-DMMP flame-retardant were 650.9 kW m -2 and 79.4 MJ m -2 respectively, in the range of 0 °C - 650 °C, which are 19.6 ± 2% and 19.1 ± 5% lower than that of pure EP within the same temperature range. Considering the significant enhancement of its flame retardancy with only a slight dosage of CMP-HSs-DMMP, such CMP hollow sphere-based flame-retardant composites may have great potential as functional bulk materials or coatings in a variety of fireproofing applications., 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 © 2020 Elsevier Inc. All rights reserved.)

The construction of photothermal materials with ideal salt tolerance has been a major subject for efficient solar desalination. Herein, a novel photothermal material based on porous ionic polymers (PIPs) nanowires is synthesized by Sonogashira-Hagihara cross-coupling reaction using ionic salt and alkynylbenzene as building blocks. The PIPs nanowires monolith shows abundant porosity with low density, leading a superior thermal insulation. The intrinsic superhydrophilicity of PIPs nanowires endows it with desired water transportation ability. By facile spraying Chinese carbon-ink on the PIPs nanowires monolith, its light absorption can be enhanced to be 90%. Based on these merits, the PIPs nanowires based photothermal materials show high solar energy conversion efficiency (81% under 1 sun irradiation). More interestingly, its inherently ionic framework can result in an ion-ion interaction between the external ions in water and ionic groups in PIPs framework, thus leading to excellent desalination ability by combing its unique superhydrophilicity, for example, no salt accumulation is observed after 6 h duration at 1 sun irradiation. Compared with the existing salt-resistant photothermal materials, the method takes the advantage of the intrinsically ionic feature of PIPs without using any artificial process, thus may open a new way for design and fabrication of high-performance salt-rejection photothermal materials., (© 2020 Wiley-VCH GmbH.)

In dense canopy, a reduction in red to far-red (R/FR) light ratio triggers shade avoidance responses (SARs) in Arabidopsis thaliana, a shade avoiding plant. Two red/far-red (R/FR) light photoreceptors, PHYB and PHYA, were reported to be key negative regulators of the SARs. PHYB represses the SARs under normal light conditions; however, the role of PHYA in the SARs remains elusive. We set up two shade conditions: Shade and strong Shade (s-Shade) with different R/FR ratios (0.7 and 0.1), which allowed us to observe phenotypes dominated by PHYB- and PHYA-mediated pathway, respectively. By comparing the hypocotyl growth under these two conditions with time, we found PHYA was predominantly activated in the s-Shade after prolonged shade treatment. We further showed that under s-Shade, PHYA inhibits hypocotyl elongation partially through repressing the brassinosteroid (BR) pathway. COP1 and PIF4,5 act downstream of PHYA. After prolonged shade treatment, the nuclear localization of COP1 was reduced, while the PIF4 protein level was much lower in the s-Shade than that in Shade. Both changes occurred in a PHYA-dependent manner. We propose that under deep canopy, the R/FR ratio is extremely low, which promotes the nuclear accumulation of PHYA. Activated PHYA reduces COP1 nuclear speckle, which may lead to changes of downstream targets, such as PIF4,5 and HY5. Together, these proteins regulate the BR pathway through modulating BES1/BZR1 and the expression of BR biosynthesis and BR target genes., (© 2020 Society for Experimental Biology and John Wiley & Sons Ltd.)

Rationale: Midodrine is widely used in the treatment of hypotensive states, there have been no reports of myoclonus associated with midodrine use in hypotension with chronic kidney disease., Patient Concerns: We report a 58-year-old female patient with chronic kidney disease (CKD) presenting with involuntary tremor 2 h after taking midodrine, which became more frequent after 6 h. Brain CT and neurological examination did not yield findings of note. Blood chemistry showed serum albumin of 3.1 g/L, ALT of 19 U/L, AST of 22 U/L, SCr of 273.9 μmol/L, K of 2.94 mmol/L, Ca of 1.63 mmol/L, and Mg of 0.46 mmol/L. Her BP was maintained at 83-110/56-75 mmHg. Her urine volume was 600-1000 mL/d, and her heart rate was within a range of 90-100 beats/min., Diagnosis: Chronic kidney disease (CKD), hypotension, metabolic acidosis, hypocalcemia, hypokalemia, and hypomagnesemia., Interventions: Midodrine treatment was stopped and the patient was treated with intravascular rehydration and furosemide. Myoclonus ceased one day after midodrine withdrawal., Lessons: Oral midodrine is widely used in the treatment of orthostatic hypotension, recurrent reflex syncope and dialysis-associated hypotension and the adverse effects are mostly mild. However, clinicians should be alert for midodrine-induced myoclonus, especially in patients with CKD.

Background: Acute myocardial infarction (AMI) occurs when atherosclerotic lesions which present in the coronary arteries cause the intravascular plate to rupture and with the result of myocardial ischemia, hypoxia, and infarct. The preferred treatment for AMI is currently percutaneous coronary intervention (PCI), for which the key to the success is the choice of anticoagulant and thrombolytic drugs during surgery. Here, we aim to explore the effects of atorvastatin combined with bivalirudin on coagulation function, cardiac function, and inflammatory factors in elderly patients with AMI who underwent PCI., Methods: The clinical data of 86 AMI patients who were admitted to our hospital between February 2016 and May 2018 were retrospectively analyzed. Based on different treatments, the patients were divided into the control group and the observation group, with 43 patients in each group. The control group patients were treated with bivalirudin, and the observation group was treated with bivalirudin plus atorvastatin. Both groups of patients underwent PCI and the clinical efficacy, coagulation function, cardiac function, inflammatory factor levels and cardiovascular events (MACE), and other clinical data were compared between the groups., Results: The total clinical effective rate in the observation group was significantly higher than that in the control group (90.90% vs. 72.09%) (P<0.05). Fibrinogen (Fg) and D-dimer (D-D) levels were significantly decreased after treatment in both groups but were significantly lower in the observation group than in the control group. The prothrombin time (PT) was significantly prolonged after treatment in both groups but was significantly longer in the observation group than in the control group after treatment (P<0.05). Meanwhile, the left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD) were significantly reduced after treatment in both groups but were significantly lower in the observation group than in the control group, whereas the left ventricular ejection fraction (LVEF) was significantly higher in the observation group compared with the control group after treatment (P<0.05). After treatment, serum levels of transforming growth factor-β1 (TGF-β1), tumor necrosis factor-α (TNF-α), and IL-6 were significantly reduced in both groups but the levels were significantly lower in the observation group than in the control group (P<0.05). The overall incidence of MACE in the observation group was significantly lower than that in the control group (9.30% vs. 30.23%) (P<0.05)., Conclusions: Atorvastatin combined with bivalirudin can improve the efficiency of clinical treatment in elderly AMI patients who undergo PCI, while simultaneously improving blood coagulation function and reducing the occurrence of bleeding, compared with bivalrudin alone. It can also decrease the level of inflammatory factors, promote vascular recanalization, and improve myocardial ischemia, thereby reducing the incidence of MACE and improving patient prognosis.

In this work, we report the synthesis of silicon aerogel elastomers (SAEs) by one-pot hydrolytic condensation of silanes, followed by drying at room temperature. The as-synthesized SAE features excellent flexibility and mechanical robustness, for example, a high compressive strength of up to 40 kPa at 75% strain was achieved. Combined with their thermal insulation properties (a low thermal conductivity of ca . 0.02 W m -1 K -1 in air), for the first time, such SAEs were used as a porous platform for both flame-retardant measurement and solar steam generation. By coating with Mg(OH) 2 via a facile coprecipitation method, the treated SAEs show excellent flame retardancy with a peak heat release rate of 25.61 kW m -2 , in addition to high fire resistance and excellent smoke suppression. When used as a solar steam generator, their evaporation efficiency was measured to be 82.7% (1 kW m -2 ), which could compete with that of other high-performance bilayered photothermal materials reported so far. Taking advantage of their simple and cost-efficient manufacture and superior mechanical robustness and flexibility, such SAEs with multifunctionalities may have great potential for a wide variety of energy-saving applications, for example, especially for thermal insulation coatings with better flame retardancy and efficient solar steam generation for desalination or freshwater production., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Objectives: Oral lichen planus (OLP) is a chronic inflammatory condition with an unclear pathological mechanism. IκB kinase α (IKKα)-regulated mammary serine protease inhibitor (MASPIN) has been shown to mediate inflammation, particularly in cancers. Here, we explored the expression of MASPIN in OLP and its role in the inflammatory response., Materials and Methods: Immunohistochemistry staining and reverse transcription-polymerase chain reaction assays were used to detect the subcellular localization and expression of MASPIN and IKKα in OLP and healthy control tissues. Levels of the inflammatory factors were compared with enzyme-linked immunosorbent assays. MASPIN and IKKα were overexpressed and silenced, respectively, in an inflammation model of human oral keratinocytes (HOKs) stimulated with lipopolysaccharide (LPS)., Results: Mammary serine protease inhibitor expression was down-regulated, whereas IKKα expression was up-regulated in OLP tissues (p < 0.01). The levels of tumour necrosis factor-alpha and interleukin-6 in OLP tissues were increased compared to those of healthy controls (p < 0.01). MASPIN overexpression in LPS-stimulated HOK cells inhibited the levels of IKKα and the secretion of inflammatory cytokines. By contrast, IKKα silencing promoted the expression of MASPIN and inhibited the secretion of inflammatory cytokines., Conclusion: Both MASPIN and IKKα are involved in the inflammatory process of OLP, suggesting potential therapeutic targets., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.)

Effects of salicylic acid (SA) on gibberellin (GA) homeostasis, C-repeat/dehydration-responsive element binding factor (CBF) pathway, and antioxidant enzyme systems linked to chilling- and oxidative-stress tolerance in tomato fruit were investigated. Mature green tomatoes (Solanum lycopersicum L. cv. Moneymaker) were treated with 0, 0.5, and 1 mM SA solution for 15 min before storage at 4 °C for 28 days. In comparison to 0 or 0.5 mM SA, 1 mM SA significantly decreased the chilling injury (CI) index in tomato fruit. In the SA-treated fruit, the upregulation of GA biosynthetic gene (GA3ox1) expression was followed by gibberellic acid (GA 3 ) surge and DELLA protein degradation. CBF1 participated in the SA-modulated tolerance and stimulated the expression of GA catabolic gene (GA2ox1). Furthermore, 1 mM SA enhanced activities of antioxidant enzymes and, thus, reduced reactive oxygen species accumulation. Our findings suggest that SA might protect tomato fruit from CI and oxidative damage through regulating GA metabolism, CBF1 gene expression, and antioxidant enzyme activities.

Porcine interferon-induced protein with tetratricopeptide repeats 3 (poIFIT3) is one of the genes most abundantly induced by IFN-α/β and swine influenza virus (SIV). However, little information is available about the role of poIFIT3 in host defense among pigs. In this study, we detected the upregulation of poIFIT3 in porcine alveolar macrophages (PAM) infected with SIV and subsequently cloned poIFIT3 from poly(I:C)-treated PAM cells. The overexpression of poIFIT3 can efficiently suppress the replication of SIV, whereas knockdown of poIFIT3 increases SIV replication. Further experiments on the functional domains showed that the C-terminal of poIFIT3 plays the main role in the antiviral activity of poIFIT3. Moreover, poIFIT3 can significantly enhance poly(I:C)-induced IFN-β promoter activity through both IRF3- and NF-κB-mediated signaling pathways. poIFIT3 potentiates IFN-β production by targeting MAVS, which was further verified by co-immunoprecipitation. This study suggests that poIFIT3 plays a significant role in the clearance of SIV in pigs and potentiates IFN-β production., (Copyright © 2014. Published by Elsevier Ltd.)

Irritable bowel syndrome (IBS) is induced by dysfunction of central nervous and peripheral intestinal systems, which affects an estimated 10-15% population worldwide annually. Stress-related psychiatric disorders including depression and anxiety are often comorbid with gastrointestinal function disorder, such as IBS. However, the mechanism of IBS still remains unknown. Curcumin is a biologically active phytochemical presents in turmeric and has pharmacological actions that benefit patients with depression and anxiety. Our study found that IBS rats showed depression- and anxiety-like behaviors associated with decreased 5-HT (serotonin), BDNF (Brain-derived neurotrophic factor) and pCREB (phosphorylation of cAMP response element-binding protein) expression in the hippocampus after chronic acute combining stress (CAS). However, these decreased parameters were obviously increased in the colonic after CAS. Curcumin (40 mg/kg) reduced the immobility time of forced swimming and the number of buried marbles in behavioral tests of CAS rats. Curcumin also decreased the number of fecal output and abdominal withdrawal reflex (AWR) scores in response to graded distention. Moreover, curcumin increased serotonin, BDNF and pCREB levels in the hippocampus, but they were decreased in the colonic of CAS rats. 5-HT(1A) receptor antagonist NAN-190 reversed the effects of curcumin on behaviors and the changes of intestine, pCREB and BDNF expression, which are related to IBS. These results suggested that curcumin exerts the effects on IBS through regulating neurotransmitters, BDNF and CREB signaling both in the brain and peripheral intestinal system.

Major depression is characterized by dysfunction of neuroendocrine and immune networks. Trans-resveratrol, a phenolic compound presented in polygonum cuspidatum, was demonstrated previously to exert antidepressant-like effects through regulating monoaminergic system, oxidative/antioxidant defense and inflammatory response. The present study investigated the synergistic antidepressant-like effect of trans-resveratrol and piperine, a bioavailability enhancer, in mice and explored the possible mechanism. Trans-resveratrol was shown to reduce the immobility time both in the tail suspension and forced swimming tests (TST and FST). But the maximal inhibition was nearly 60% even if the doses were increased by 160 mg/kg; while piperine produced weak antidepressant-like effects in these two models. The interaction between trans-resveratrol and piperine was shown a clear-cut synergistic effect as evidenced by an isobolographic analysis. The further study suggested that the anti-immobility response from the subthreshold dose of piperine (2.5 mg/kg) and low doses of trans-resveratrol (10 and 20 mg/kg) was abolished by pretreatment with para-chlorophenylalanine (PCPA, 300 mg/kg, i.p.) in TST and FST, indicating the involvement of serotonergic system. Moreover, treatment with the subthreshold dose of piperine and low doses of trans-resveratrol attenuated reserpine-induced hypothermia and ptosis arguing for the relevance of noradrenaline. Additional evidence from neurochemical (monoamines in the frontal cortex, hippocampus, and hypothalamus) and biochemical (monoamine oxidase, MAO activity) assays corroborated the synergistically elevated monoaminergic system after co-treatment with trans-resveratrol and piperine. The present results indicate the effect of trans-resveratrol combined with piperine on depressive-like behaviors may be partly due to the potentiated activation of monoaminergic system in the brain. Further studies are necessary to elucidate the involvement of the oxidative/nitrosative stress, inflammatory and neuroprotective pathway in the antidepressant-like effect of this combination. The synergistic effect obtained from the combination may provide innovative clues for designing novel antidepressants with high efficacy and low side effects.

A Δ6-desaturase gene was isolated from Microula sikkimensis. Sequence analysis indicated that the gene, designated MsD6DES, had an open reading frame of 1,357 bp and encoded 448 amino acids. Heterologous expression in tobacco indicated that MsD6DES can use endogenous substrates to synthesize γ-linolenic acid (GLA, 18:3(Δ 6,9,12)) and octadecatetraenoic acid (OTA, 18:4(Δ 6,9,12,15)). MsD6DES transcripts were distributed in all tested tissues, with high expression levels in seeds and young leaves. The effects of temperature and wounding stresses on MsD6DES expression were analyzed. The results indicated that temperature regulates MsD6DES at the transcriptional level. MsD6DES expression increased first, reaching a maximum 4 h after low-temperature treatment. A slight increase in MsD6DES transcript levels was also observed under high temperature. We found that the response of MsD6DES to temperature stress was different from those of fungi and algae. In addition, MsD6DES was found to be wound-inducible.

Background: As a mild, highly contagious, respiratory disease, swine influenza always damages the innate immune systems, and increases susceptibility to secondary infections which results in considerable morbidity and mortality in pigs. Nevertheless, the systematical host response of pigs to swine influenza virus infection remains largely unknown. To explore it, a time-course gene expression profiling was performed for comprehensive analysis of the global host response induced by H1N1 swine influenza virus in pigs., Results: At the early stage of H1N1 swine virus infection, pigs were suffering mild respiratory symptoms and pathological changes. A total of 268 porcine genes showing differential expression (DE) after inoculation were identified to compare with the controls on day 3 post infection (PID) (Fold change ≥ 2, p < 0.05). The DE genes were involved in many vital functional classes, mainly including signal transduction, immune response, inflammatory response, cell adhesion and cell-cell signalling. Noticeably, the genes associated with immune and inflammatory response showed highly overexpressed. Through the pathway analysis, the significant pathways mainly concerned with Cell adhesion molecules, Cytokine-cytokine receptor interaction, Toll-like receptor signaling pathway and MAPK signaling pathway, suggesting that the host took different strategies to activate these pathways so as to prevent virus infections at the early stage. However, on PID 7, the predominant function classes of DE genes included signal transduction, metabolism, transcription, development and transport. Furthermore, the most significant pathways switched to PPAR signaling pathway and complement and coagulation cascades, showing that the host might start to repair excessive tissue damage by anti-inflammatory functions. These results on PID 7 demonstrated beneficial turnover for host to prevent excessive inflammatory damage and recover the normal state by activating these clusters of genes., Conclusions: This study shows how the target organ responds to H1N1 swine influenza virus infection in pigs. The observed gene expression profile could help to screen the potential host agents for reducing the prevalence of swine influenza virus and further understand the molecular pathogenesis associated with H1N1 infection in pigs.

We report a comprehensive theoretical study on the decarbonylation of acetaldehyde by Fe+ and Cr+. Various intermediates, transition states, and products involved in the decarbonylation reactions are fully optimized at the B3LYP/6-311+G(2df,2pd) level of theory. The potential energy surfaces (PESs) corresponding to [M,O,C2,H4]+(M=Cr and Fe) are examined in detail using B3LYP and CCSD(T) methods, respectively. The validity of these theoretical methods is calibrated with respect to the available thermochemical data. Calculations suggest that the Cr+ mediated decarbonylation of acetaldehyde takes place in four steps on the sextet surface: encounter complexation, C-C activation, aldehyde H-shift, and nonreactive dissociation, in good accordance with the Co+ mediated decarbonylation of acetaldehyde [Zhao, Zhang, Guo, Wu, Lu, Chem. Phys. Lett. 2005, 414, 28], while for the Fe+/acetaldehyde system decarbonylation can occur on both the quartet and the sextet PESs. The quartet pathway, which experiences spin-orbit coupling between the two surfaces, is energetically more favorable; whereas along the sextet decarbonylation coordinate several high-energy barriers are revealed. The theoretical results are compared with the experimental product kinetic energy and angular distributions of decarbonylation of acetaldehyde by Fe+ and Cr+ measured using a crossed-beam technique [Sonnenfroh, Farrar, J. Am. Chem. Soc. 1986, 108, 3521].