Preventive and therapeutic effects of rifaximin on hepatic encephalopathy with differential application dosages and strategies: a network meta-analysis.

BACKGROUND: Hepatic encephalopathy (HE) is a neuropsychiatric syndrome that affects the prognosis of patients with liver disease and is considered an independent risk factor for hospitalization and death. Rifaximin has been approved for HE treatment. This review will analyze the effect of rifaximin on different stages of HE with differential application dosages and strategies by traditional and network meta-analyses. METHODS: We performed a systematic search of PubMed, EmBase, and Cochrane Library databases up to February 26, 2023, to identify randomized controlled trials (RCTs) about rifaximin for the prevention and treatment of HE. The outcomes included incidence of HE and HE progression, HE reversal, mortality, and adverse effects. RESULTS: A total of 21 studies were included. In the primary prevention of HE, rifaximin significantly reduced the incidence of HE (OR: 0.66; 95% CI: 0.45, 0.96; p = 0.032). In secondary prevention, rifaximin significantly reduced the risk of recurrence in patients who were in remission (OR: 0.38; 95% CI: 0.28, 0.52; p < 0.001). In the treatment of minimal HE, rifaximin significantly reduced the breakthrough of MHE to OHE (OR: 0.17; 95% CI: 0.04,0.63; p = 0.008). Rifaximin also significantly improved the clinical symptoms of MHE and OHE patients (OR: 3.76; 95% CI: 2.69, 5.25; p < 0.001). However, rifaximin did not reduce mortality at any stage in HE patients (OR: 0.79; 95% CI: 0.58, 1.08; p = 0.133). Additionally, rifaximin did not increase the risk of adverse effects (OR: 0.96; 95% CI: 0.74, 1.24; p = 0.749). In the network meta-analysis, the 400 mg T.I.D. intervention had a relative advantage for HE risks in primary and secondary prevention. In the treatment of MHE, 600 mg b.i.d. was superior in preventing the breakthrough from MHE to OHE. CONCLUSION: Rifaximin prevented HE risks and progression and improved clinical symptoms in patients with MHE but did not reduce mortality. For primary and secondary prevention, 400 mg t.i.d. could be considered. 600 mg b.i.d. could be considered in patients with MHE.

CD4+CCR8+ Tregs in ovarian cancer: a potential effector Tregs for immune regulation.

BACKGROUND: Tregs are key drivers of immunosuppression in solid tumors. As an important chemokine receptor on Tregs, the regulatory effect of CCR8 on tumor immunity has received more and more attention. However, the current research on CCR8 in the immune microenvironment of ovarian cancer has not been clear. METHODS: Bioinformatics analysis was used to compare the transcriptome differences between CD4+ T cells in the peripheral circulation and infiltrated in ovarian tumor tissues. RT-PCR was used to detect the expression levels of chemokine receptor-related differential genes on CD4+ T cells in peripheral blood and ovarian tumor tissues. Multiparameter flow cytometry was used to detect the proportion and phenotypic characteristics of CD4+CCR8+ Tregs and CD4+CCR8- Tregs in different sample types. The expression level of CCR8 ligands was detected at multiple levels. To explore the important role of CCR8-CCL1 and CCR8-CCL18 axis in the migration and invasion of CD4+CCR8+ Tregs into ovarian tumor tissues by establishing a chemotaxis system in vitro. RESULTS: In this study, significantly different gene expression profiles were found between peripheral circulating CD4+ T cells and infiltrating CD4+ T cells in ovarian tumor tissues, in which chemokine-chemokine receptor signaling pathway was significantly enriched in all three groups of differential genes. The expression level of CCR8 in infiltrating CD4+ T cells of ovarian cancer tissue was significantly higher than that in peripheral blood of healthy controls and ovarian cancer patients, and high expression of CCR8 was significantly correlated with advanced tumor stage and poor differentiation. CD4+CCR8+ Tregs are the main type of infiltrating CD4+ Tregs in ovarian tumor tissues, which have stronger immunosuppressive phenotypes, secrete more inhibitory cytokines and have stronger proliferation ability. The ligands CCL1 and CCL18 corresponding to CCR8 were significantly overexpressed in ovarian tumor tissues, and the CCR8-CCL1 and CCR8-CCL18 axis played a key role in the migration and infiltration of CD4+CCR8+ Tregs into ovarian tumor tissues. CONCLUSIONS: The results of this study may help to understand the phenotypic characteristics and recruitment process of Tregs in the tumor, and provide new ideas for improving the immunosuppressive status of the ovarian cancer microenvironment.

Prognostic Factors and a Predictive Nomogram of Cancer-Specific Survival of Epithelial Ovarian Cancer Patients with Pelvic Exenteration Treatment.

Objective: The aim of this study was to explore prognostic factors, develop and internally validate a prognostic nomogram model, and predict the cancer-specific survival (CCS) of epithelial ovarian cancer (EOC) patients with pelvic exenteration (PE) treatment. Methods: A total of 454 EOC patients from the Surveillance, Epidemiology, and End Results (SEER) database were collected according to the inclusion criteria and randomly divided into the training (n = 317) and validation (n = 137) cohorts. Prognostic factors of EOC patients with PE treatment were explored by univariate and multivariate stepwise Cox regression analyses. A predictive nomogram was constructed based on selected risk factors. The predictive power of the constructed nomogram was assessed by the time-dependent receiver operating characteristic (ROC) curve. Kaplan-Meier (KM) curve stratified by patients' nomoscore was also plotted to assess the risk stratification of the established nomogram. In internal validation, the C index, calibration curve, and decision curve analysis (DCA) were employed to assess the discrimination, calibration, and clinical utility of the models, respectively. Results: In the training cohort, age, histological type, Federation of Gynecology and Obstetrics (FIGO) stage, number of examined lymph nodes, and number of positive lymph nodes were found to be independent prognostic factors of postoperative CSS. A practical nomogram model of EOC patients with PE treatment was constructed based on these selected risk factors. Time-dependent ROC curves and KM curves showed the superior predictive capability and excellent clinical stratification of the nomogram in both training and validation cohorts. In the internal validation, the C index, calibration plots, and DCA in the training and validation cohorts confirmed that the nomogram presents a high level of prediction accuracy and clinical applicability. Conclusion: Our nomogram exhibited satisfactory survival prediction and prognostic discrimination. It is a user-friendly tool with high clinical pragmatism for estimating prognosis and guiding the long-term management of EOC patients with PE treatment.

Encapsulation of a metal-organic cage-based porous salt in silica nanopores.

A metal-organic cage (MOC)-based porous salt composed of cationic Zr-MOC and anionic Cu-MOC was incorporated into SBA-15 nanopores via a two-step impregnation method for the first time. The encapsulated MOC-based porous salt showed improved iodine adsorption capacity when compared with the bulk sample.

Glucose metabolism and function of CD4+ Tregs are regulated by the TLR8/mTOR signal in an environment of SKOV3 cell growth.

PURPOSE: To investigate the role of mammalian target of rapamycin (mTOR) signal in Toll-like receptor (TLR) 8-mediated regulation of glucose metabolism and its effect on reversing immunosuppression in CD4+ regulatory T-cells (Tregs) in ovarian cancer (OC). METHODS: Fluorescence-activated cell sorting was used to detect the expression levels of mTOR+ and 4E-BP1+ cells in CD4+ Tregs. The prognosis and immune infiltration analysis of mTOR mRNA in OC were performed using the TIMER and Kaplan-Meier plotter database. Furthermore, real-time polymerase chain reaction (RT-PCR) and western blot (WB) were used to detect expression levels of glucose metabolism-related genes and proteins in CD4+ Tregs. Glucose uptake and glycolysis levels were detected by colorimetry, while the effects of CD4+ Tregs on the proliferation of CD4+ T-effector cells (Teffs) were evaluated by carboxyfluorescein diacetate succinimidyl ester (CFSE). RESULTS: mTOR expression in CD4+ Tregs was significantly higher in patients with OC compared with controls and in CD4+ Tregs than in CD4+ Teffs in OC. Additionally, the expression level of mTOR mRNA was related to prognosis and immune infiltration levels in patients with OC. Blocking the mTOR signal resulted in downregulation of glucose metabolism in CD4+ Tregs. Simultaneous inhibition of the mTOR signal while activation of the TLR8 signal had a coordinated inhibitory effect on glucose metabolism and the immunosuppressive function of CD4+ Tregs. Furthermore, the mTOR signal played an essential role in TLR8-mediated reversal of immunosuppressive function in CD4+ Tregs. CONCLUSION: These findings imply that activation of the TLR8 signal inhibits glucose metabolism in CD4+ Tregs by downregulating mTOR signaling, thereby reversing the immunosuppressive function of these cells in an OC cell growth environment.

Circulating CD4+ Treg, CD8+ Treg, and CD3+ γδ T Cell Subpopulations in Ovarian Cancer.

Background and Objectives: Regulatory T cells (Tregs) are usually enriched in ovarian cancer (OC), and their immunosuppressive function plays a key role in tumorigenesis and progression. We mainly explored the phenotypical characterization of Treg-related markers on αß and γδ T cell subsets in patients with OC. Materials and Methods: Thirty-six untreated patients with OC at the Women's Hospital of Nanjing Medical University from September 2019 to August 2021 were enrolled. Phenotypical characterization of Tregs-related markers were detected by flow cytometry (FCM). Enzyme-linked immunosorbent assay was used to detect the levels of carbohydrate antigen (CA125) and transforming growth factor ß (TGF-ß). The level of human epididymis protein 4 (HE4) was detected by electrochemiluminescence immunoassay. Results: Circulating CD4+ Tregs, CD8+ Tregs, and CD3+γδ T cell subpopulations from OC patients have elevated Foxp3, CD25, CD122, Vδ1, and reduced CD28 expression compared to benign ovarian tumor (BOT) patients and healthy controls (HC). The upregulation of Foxp3 and Vδ1 and the downregulation of CD28 were highly specific for maintaining the immunosuppression function of CD4+ Tregs, CD3+γδ T cells, and CD8+ Tregs in OC patients. These Treg subpopulations were able to discriminate OC from BOT and HC. The levels of CA125, HE4, and TGF-ß were increased in OC patients. A significant positive correlation between Treg subpopulations and CA125, HE4, and TGF-ß was revealed. Conclusions: Proportions of CD4+ Tregs, CD8+ Tregs, and CD3+γδ T cell subsets were significantly increased in OC patients and were positively correlated with FIGO stage/metastasis status, CA125, HE4, and TGF-ß. These indicators have the potential to be used as immunosurveillance biomarkers for OC.

Enhancing Cutaneous Wound Healing Based on Human Induced Neural Stem Cell-derived Exosomes.

Background: Wound healing of skin is a complicated process. Cutaneous innervation and neurotrophic factors could participate in multiple stages of wound healing. Neurotrophic factors are mainly produced and released by neurons and neural stem cells (NSCs) which could be obtained in large quantities from human-induced pluripotent stem cells (iPSCs) in vitro. However, the potential wound healing effects of NSC secretions, such as exosomes, are unexplored yet. Methods: NSCs-derived exosomes (NSC-exo) and iPSCs-derived exosomes (iPSC-exo) were isolated from the cell culture supernatants by centrifugation, and then quantified and characterized. The effects of these exosomes on the migration of human dermal fibroblasts (HDF) cells and the tube formation of human umbilical vein endothelial cells (HUVECs) were investigated in vitro. And the in vivo wound healing effect of these exosomes were tested on the mouse skin trauma model. Therefore, a dipeptide/hyaluronic acid (Nap-FF/HA) composite hydrogel was used to encapsulate the exosomes as a sustained release carrier. Histological observations were performed to evaluate the wound healing effect of exosomes. Furthermore, the non-labeling proteomic analysis was performed to explore the possible mechanisms of NSC-exo on wound healing. Results: We obtained extracellular vesicles in a bowl-like structure with membranes which meet the general standards of exosomes. NSC-exo showed promotion effect on the migration of HDF cells and the tube formation of HUVECs in vitro. In a mouse skin injury model, NSC-exo enhanced the wound healing and the Nap-FF/HA hydrogel that contained exosomes did so with less drug frequency by sustaining release of exosomes. Further proteomic analysis demonstrated that the carried neurotrophic factors and immunity-related proteins in NSC-exo may play a functional role in wound healing. Conclusion: NSC-exo may enhance wound healing via neurotrophic factors and immunomodulation.

Strategies for the Construction of Functional Materials Utilizing Presynthesized Metal-Organic Cages (MOCs).

Metal-organic cages (MOCs) that assemble from metal ions or metal clusters and organic ligands have attracted the interest of the scientific community because of their various functional coordination cavities. Unlike metal-organic frameworks (MOFs) with infinite frameworks, MOCs have discrete structures, making them soluble and stable in certain solvents and facilitating their application as starting reagents in the further construction of single components or composite materials. In recent years, increasing progress has been made in this field. In this review, we introduce these works from the perspective of design strategies, and focus on how presynthesized MOCs can be used to construct functional materials. Finally, we discuss the challenges and development prospects in this field.

Distribution and Clinical Significance of IL-17A in Tumor-Infiltrating Lymphocytes of Non-Small Cell Lung Cancer Patients.

Objective: To investigate the distribution of IL-17A and its clinical significance in tumor infiltrating lymphocytes (TILs) of patients with non-small cell lung cancer (NSCLC). Methods: Expression level of IL-17A in TILs of 3 paired NSCLC and paracancerous specimens was measured by qRT-PCR. The distribution of IL-17A in immune cell subsets of 15 paired NSCLC and paracancerous specimens was examined by flow cytometry. The correlation between IL-17A and clinical features of NSCLC was identified. Results: IL-17A was significantly upregulated in TILs of NSCLC specimens than those of paracancerous ones (p < 0.0001). Meanwhile, T helper 17 cells (Th17 cells, p < 0.001), IL-17-secreting CD8+ T cells (Tc17 cells, p < 0.001) and IL-17-producing cells (γδT17 cells, p < 0.0001) were significantly abundant in TILs of NSCLC specimens than those of controls, and the higher abundance of the latter was much pronounced than that of the former two. Moreover, γδT17 cells in TILs were significantly correlated with lymphatic metastasis and CYFRA 21-1 level of NSCLC patients (p < 0.05). Conclusion: Tumor infiltrated γδT cells are the main source of IL-17 in early-stage NSCLC, and IL-17 may be a vital regulator involved in the development of NSCLC.

An integrative pan-cancer analysis of molecular characteristics and oncogenic role of mitochondrial creatine kinase 1A (CKMT1A) in human tumors.

In recent years, several studies have suggested that mitochondrial creatine kinase 1A (CKMT1A) plays a key role in various cancer types. However, there is still a lack of systematic understanding of the contribution of CKMT1A in different types of cancer. Therefore, this study aims to explore the potential role of CKMT1A in human tumors. Firstly, we evaluated the expression level of CKMT1A in 33 types of tumors. Secondly, we used the GEPIA2 and Kaplan-Meier plotter to explore the relationship between CKMT1A expression and survival prognosis. Furthermore, the genetic alterations of CKMT1A were analyzed by the cBioPortal web. In addition, we performed immune infiltration analysis and gene enrichment pathway analysis. CKMT1A was highly expressed in most types of cancers and there was a significant correlation between CKMT1A expression and the prognosis of patients for certain tumors. Non-Small Cell Lung Cancer cases with altered CKMT1A showed a poorer overall survival. CKMT1A expression was negatively correlated with the infiltration of cancer-associated fibroblasts in most tumors. We also found that its expression was negatively associated with CD8+ T-cell infiltration in several tumors. Furthermore, enrichment analysis revealed that "Glycolysis/ Gluconeogenesis" and "metabolic pathways" functions were involved in the functional mechanism of CKMT1A. Taken together, our studies will provide a relatively clear and integrative understanding of the role of CKMT1A across different tumors. All these findings will lay a solid foundation for further molecular assays of CKMT1A in tumorigenesis and provide the rationale for developing novel therapeutic strategies.

Global prevalence of occult hepatitis B: A systematic review and meta-analysis.

The study aimed to investigate the prevalence and risk factors associated with occult hepatitis B virus (HBV) infection (OBI) in the global population. We searched PubMed, Embase, CINAHL, Cochrane and Web of Science from database inception through 27 Dec, 2018. Studies reporting HBV-DNA serological data in previously undiagnosed hepatitis B patients were included. The data were further categorized according to the presence of risk factors. After an initial screening of 2,325 records, we finally included 98 articles about the prevalence of OBI from 34 countries and regions. The OBI prevalence was 0.82% (95% CI:0.69-0.96) in the general population, 16.26% (95% CI:10.97-22.34) in HIV patients, 13.99% (95% CI:8.33-20.79) in patients with other liver diseases, 4.25% (95% CI:1.64-7.87) in haemodialysis patients and 5.14% (95% CI:2.26-9.01) patients with other risk factors. In conclusion, OBI prevalence varies significantly across different populations and nations, which deserve attention from the public health authorities. Our results generate further epidemiological data to identify the population with OBI, which has important clinical implications in finding these high-risk populations to design preventive and management strategies.

CoQ10 enhances the efficacy of airway basal stem cell transplantation on bleomycin-induced idiopathic pulmonary fibrosis in mice.

BACKGROUND: Recent studies have demonstrated that airway basal stem cells (BCs) transplantation can ameliorate bleomycin-induced idiopathic pulmonary fibrosis (IPF) through lung regeneration promotion. However, BCs under oxidative stress in the alveolar microenvironment are poor in survival, causing unsatisfied efficacy of BCs transplantation. In this study, we investigated whether Coenzyme Q10(CoQ10) counteracts oxidative stress in the alveolar microenvironment, thus improved the efficacy of BCs transplantation for IPF treatment. METHODS: The protective effects of CoQ10 on H2O2-induced BCs apoptosis and cytoplasmic reactive oxygen species (ROS) level were tested by flow cytometry in vitro. The therapeutic effects of BCs combined with CoQ10 were compared to a single BCs transplantation protocol in IPF treatment after 2 weeks and were evaluated by parameters including changes of body weight and survival rate, as well as various levels of pulmonary inflammation, α-SMA expression and hydroxyproline (HYP) in IPF mouse lung tissues. RESULTS: CoQ10 preincubation with BCs (10 mM, 24 h) significantly reduced the late apoptosis of BCs and the number of oxidative stressful BCs as a result of H2O2 stimulation (1 mM, 6 h) in vitro. IPF mouse model was constructed through bleomycin (5 mg/kg) intratracheal instillation. Bleomycin-induced IPF mice showed weight loss continuously and mortality increased progressively during modeling. Serious pulmonary inflammatory cell infiltration, collagen fiber proliferation, and collagen protein deposition were observed in lung tissues of IPF mice. Though BCs transplantation alone improved indicators above in bleomycin-induced IPF mice to some extent, the combination with CoQ10 improved the transplantation efficacy and obtained better therapeutic effects. CONCLUSION: CoQ10 blocked H2O2-induced apoptosis of BCs and ROS production in vitro, and enhanced the efficacy of BCs transplantation against bleomycin-induced IPF in mice.

Regioisomers Salviprolin A and B, Unprecedented Rosmarinic Acid Conjugated Dinorditerpenoids from Salvia przewalskii Maxim.

Salvia przewalskii Maxim is a perennial plant from the genus Salvia (family Lamiaceae). The roots of S. przewalskii were long used as a traditional herb to treat blood circulation related illnesses in China. As part of our continuing interest in polycyclic natural products from medicinal plants, two unprecedented adducts comprised of a dinor-diterpenoid and a 9'-nor-rosmarinic acid derivative, linked by a 1,4-benzodioxane motif (1 and 2), were isolated from the roots of S. przewalskii. Their structures were established by extensive spectroscopic approaches including 1D, 2D NMR, and HRFABMS. Their cytotoxic activities against five human tumor cell lines were evaluated.

Potential impact and mechanism of Long Non-coding RNAs on cancer and associated T cells.

The discovery of many aberrant expressions of long non-coding RNAs (lncRNAs) in various cancers has focused attention on the effects of lncRNA on cancer cells themselves, including cell proliferation, growth inhibition, cell migration, cell immortality, vascular regeneration and cell viability. But with the increasing role of immunotherapy in cancer therapy, a large number of studies have revealed that the regulatory role of lncRNAs in immunity such as differentiation of immune cells can also influence the development and progression of cancer. In particular, recent publications have suggested that lncRNAs play critical roles in T-lymphocyte activation, proliferation, differentiation, function, apoptosis and metabolism. To elucidate the actual functions of lncRNAs at the molecular level of cancer pathogenesis, we summarize some of the current lncRNA regulatory mechanisms associated with T cell to discuss their effects in cancer in the hope of providing potential cancer therapeutic targets or cancer biomarkers. However, we all know that the differentiation and function of T cells is an extremely complex process that involves the expression and regulation of multiple lncRNAs. As a result, more regulatory mechanisms of lncRNAs need to be further studied.

Research Progress in Prognostic Factors and Biomarkers of Ovarian Cancer.

Ovarian cancer is a serious threat to women's health; its early diagnosis rate is low and prone to metastasis and recurrence. The current conventional treatment for ovarian cancer is a combination of platinum and paclitaxel chemotherapy based on surgery. The recurrence and progression of ovarian cancer with poor prognosis is a major challenge in treatment. With rapid advances in technology, understanding of the molecular pathways involved in ovarian cancer recurrence and progression has increased, biomarker-guided treatment options can greatly improve the prognosis of patients. This review systematically discusses and summarizes existing and new information on prognostic factors and biomarkers of ovarian cancer, which is expected to improve the clinical management of patients and lead to effective personalized treatment.

Glucose metabolism characteristics and TLR8-mediated metabolic control of CD4+ Treg cells in ovarian cancer cells microenvironment.

Immunotherapy is expected to become the most promising new treatment for ovarian cancer owing to its immunogenicity. However, immunosuppression in the tumor microenvironment is a major obstacle to the efficacy of tumor therapy. Studies have found different metabolism ways of regulatory T cells (Tregs) in the cancer environment may be related to the immunosuppression and Toll-like receptor 8 (TLR8) can reverse the suppression function of Tregs. But it is still unclear that if the TLR8-mediated function reversal is associated with the change of glucose metabolism of Tregs. It was found that the positive expression rates of Glut1, HIF-1α, and Ki67 in CD4+ Treg cells of OC were significantly higher than that in benign ovarian tumor and HC, and also significantly higher than that in CD4+ Teffs of OC. What's more, compared with CD4+ Teff group, CD4+ Tregs highly expressed seven genes and three proteins related to glucose metabolism and had higher levels of glucose uptake and glycolysis. After activating TLR8 signal of CD4+ Tregs, the proliferation level of naive CD4+ T cells was higher than that of the control group. At the same time, the expression levels of eight genes and five proteins related to glucose metabolism in CD4+ Treg cells with TLR8 activated were decreased and levels of glucose uptake and glycolysis were also lower. Furthermore, TLR8 signaling also downregulated the mTOR pathway in CD4+ Tregs. CD4+ Tregs pretreated with 2-deoxy-d-Glucose (2-DG) and galloflavin also attenuated the inhibition of Teffs proliferation. Although CD4+ Tregs pretreated with 2-DG and galloflavin before activating TLR8 signal had no significant difference compared with the group only treated with inhibitors, which suggested TLR8-mediated reversal of CD4+ Treg cells inhibitory function in ovarian cancer cells co-cultured microenvironment had a causal relationship with glucose metabolism.

Reliability of induced sputum test is greater than that of throat swab test for detecting SARS-CoV-2 in patients with COVID-19: A multi-center cross-sectional study.

We previously reported that sputum induction was more sensitive than throat swabs for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in two convalescent coronavirus disease 2019 (COVID-19) patients; however, the value and safety of induced sputum testing require further study. We conducted a prospective multi-center cross-sectional study to compare induced sputum to throat swabs for SARS-CoV-2 detection. Confirmed COVID-19 patients from six hospitals in six cities across China who received one or more negative RT-PCR result for SARS-CoV-2 were enrolled, and paired specimens (induced sputum and throat swabs; 56 cases) were assayed. In three paired samples, both the induced sputum and throat swabs were positive for SARS-CoV-2. The positive rate for induced sputum was significantly higher than for throat swabs both overall (28.6% vs 5.4%, respectively; p < 0.01). Patients were divided according to time span from onset of illness to sample collection into the more-than-30-day (n = 26) and less-than-30-day (n = 30) groups. The positive rate for induced sputum was also significantly higher than for throat swabs in the less-than-30-day group (53.3% vs 10.0%, respectively; p < 0.001). For the more-than-30-day group, all paired samples were negative for SARS-CoV-2. Blood oxygen saturation, respiratory rate, and heart rate remained stable during sputum induction and no staff were infected. Because induced sputum is more reliable and has a lower false-negative rate than throat swabs, we believe induced sputum is more useful for the confirmation of COVID-19 and is safer as a criterion for release from quarantine.

Water use strategies and drought intensity define the relative contributions of hydraulic failure and carbohydrate depletion during seedling mortality.

COMBINING HYDRAULIC: and carbon-related measurements can help elucidate drought-induced plant mortality. To study drought mortality mechanisms, seedlings of two woody species, including the anisohydric Robinia pseudoacacia and isohydric Quercus acutissima, were cultivated in a greenhouse and subjected to intense drought by withholding water and mild drought by adding half of the amount of daily water lost. Patterns of leaf and root gas exchange, leaf surface areas, growth, leaf and stem hydraulics, and carbohydrate dynamics were determined in drought-stressed and control seedlings. We detected a complete loss of hydraulic conductivity and partial depletion of total nonstructural carbohydrates contents (TNC) in the dead seedlings. We also found that intense drought triggered a more rapid decrease in plant water potential and a faster drop in net photosynthesis below zero, and a greater TNC loss in dead seedlings than mild drought. Additionally, anisohydric R. pseudoacacia suffered a rapider death than the isohydric Q. acutissima. Based on these findings, we propose that hydraulic conductivity loss and carbon limitation jointly contributed to drought-induced death, while the relative contributions could be altered by drought intensity. We thus believe that it is important to illustrate the mechanistic relationships between stress intensity and carbon-hydraulics coupling in the context of isohydric vs. anisohydric hydraulic strategies.

Antinociceptive Efficacy of Retigabine and Flupirtine for Gout Arthritis Pain.

INTRODUCTION: Gout arthritis is an inflammatory disease characterized by severe acute pain. The goal of pharmacological gout arthritis treatments is to reduce pain, and thereby increase the patient's quality of life. The Kv7/M channel activators retigabine and flupirtine show analgesic efficacy in animal models of osteoarthritic pain. We hypothesized that these drugs may also alleviate gout arthritis pain. OBJECTIVE: To determine the effects of retigabine and flupirtine on pain behavior associated with monosodium urate (MSU)-induced gout arthritis. METHODS: The gout arthritis model was established with an intra-articular injection of MSU into the right ankle joint, animals were treated with retigabine or flupirtine, and pain-related behaviors were assessed. RESULTS: Retigabine and flupirtine significantly increased the mechanical threshold and prolonged the paw withdrawal latency in a rat model of gout arthritis pain in a dose-dependent manner. The antinociceptive effects of retigabine and flupirtine were fully antagonized by the Kv7/M channel blocker XE991. CONCLUSION: Retigabine and flupirtine showed antinociceptive effects for MSU-induced gout pain at different times during pain development.

Growth and physiological responses to successional water deficit and recovery in four warm-temperate woody species.

Plant responses to drought and their subsequent rehydration can provide evidence for forest dynamics within the context of climate change. In this study, the seedlings of two native species (Vitex negundo var. heterophylla, Quercus acutissima) and two exotic species (Robinia pseudoacacia, Amorpha fruticosa) to China were selected in a greenhouse experiment. The gas exchange, stem hydraulic parameters, plant osmoprotectant contents and antioxidant activities of the seedlings that were subjected to sustained drought and rehydration (test group) as well as those of well-irrigated seedlings (control group) were measured. The two native species exhibited a greater degree of isohydry with drought because they limited the stomatal opening timely from the onset of the drought. However, the two exotic species showed a more 'water spender'-like strategy with R. pseudoacacia showing anisohydric responses and A. fruticosa showing isohydrodynamic responses to drought. Severe drought significantly decreased the leaf gas exchange rates and hydraulic properties, whereas the instantaneous water use efficiency and osmoprotectant contents increased markedly. Most of the physiological parameters recovered rapidly after mild drought rehydration, but the water potential and/or supply of nonstructural carbohydrates did not recover after severe drought rehydration. The results demonstrate that the xylem hydraulic conductivity and shoot water potential jointly play a crucial role in the drought recovery of woody plants. In brief, the native species may play a dominant role in the future in warm-temperate forests because they employ a better balance between carbon gain and water loss than the alien species under extreme drought conditions.